JP5964746B2 - Dna−細胞コンジュゲート - Google Patents
Dna−細胞コンジュゲート Download PDFInfo
- Publication number
- JP5964746B2 JP5964746B2 JP2012504866A JP2012504866A JP5964746B2 JP 5964746 B2 JP5964746 B2 JP 5964746B2 JP 2012504866 A JP2012504866 A JP 2012504866A JP 2012504866 A JP2012504866 A JP 2012504866A JP 5964746 B2 JP5964746 B2 JP 5964746B2
- Authority
- JP
- Japan
- Prior art keywords
- cell
- cells
- nucleic acid
- dna
- acid moiety
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000004027 cell Anatomy 0.000 claims description 1033
- 102000053602 DNA Human genes 0.000 claims description 227
- 108020004414 DNA Proteins 0.000 claims description 219
- 238000000034 method Methods 0.000 claims description 157
- 150000007523 nucleic acids Chemical group 0.000 claims description 154
- 108091034117 Oligonucleotide Proteins 0.000 claims description 113
- 125000000524 functional group Chemical group 0.000 claims description 75
- 108091023037 Aptamer Proteins 0.000 claims description 58
- 150000001413 amino acids Chemical class 0.000 claims description 58
- 235000001014 amino acid Nutrition 0.000 claims description 57
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 55
- 239000000758 substrate Substances 0.000 claims description 51
- 230000000295 complement effect Effects 0.000 claims description 49
- 102000039446 nucleic acids Human genes 0.000 claims description 46
- 108020004707 nucleic acids Proteins 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 34
- 235000000346 sugar Nutrition 0.000 claims description 34
- 210000002421 cell wall Anatomy 0.000 claims description 31
- 238000004519 manufacturing process Methods 0.000 claims description 28
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 22
- 239000004472 Lysine Substances 0.000 claims description 22
- 235000018977 lysine Nutrition 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 21
- 235000018417 cysteine Nutrition 0.000 claims description 19
- 210000004962 mammalian cell Anatomy 0.000 claims description 18
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 17
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 17
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 17
- 210000000130 stem cell Anatomy 0.000 claims description 16
- 238000012269 metabolic engineering Methods 0.000 claims description 14
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 12
- 235000013922 glutamic acid Nutrition 0.000 claims description 12
- 239000004220 glutamic acid Substances 0.000 claims description 12
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 11
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 11
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 11
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 11
- 235000003704 aspartic acid Nutrition 0.000 claims description 11
- 150000001540 azides Chemical class 0.000 claims description 11
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 11
- 235000004400 serine Nutrition 0.000 claims description 11
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 10
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 10
- 235000002374 tyrosine Nutrition 0.000 claims description 10
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 8
- 239000004473 Threonine Substances 0.000 claims description 8
- 235000008521 threonine Nutrition 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 claims 1
- 230000027455 binding Effects 0.000 description 90
- 239000000243 solution Substances 0.000 description 80
- 108090000623 proteins and genes Proteins 0.000 description 61
- 239000000523 sample Substances 0.000 description 61
- 238000004458 analytical method Methods 0.000 description 59
- 229940024606 amino acid Drugs 0.000 description 56
- 230000014509 gene expression Effects 0.000 description 55
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 50
- 239000002953 phosphate buffered saline Substances 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 47
- 108091006146 Channels Proteins 0.000 description 43
- 239000011521 glass Substances 0.000 description 43
- 210000000234 capsid Anatomy 0.000 description 42
- 102000004169 proteins and genes Human genes 0.000 description 41
- 230000008569 process Effects 0.000 description 38
- 239000000446 fuel Substances 0.000 description 37
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 36
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 36
- 239000002609 medium Substances 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 36
- 239000000126 substance Substances 0.000 description 36
- 230000004048 modification Effects 0.000 description 35
- 238000012986 modification Methods 0.000 description 35
- 238000005259 measurement Methods 0.000 description 34
- 239000012091 fetal bovine serum Substances 0.000 description 32
- 238000004630 atomic force microscopy Methods 0.000 description 31
- 239000010410 layer Substances 0.000 description 30
- 239000002585 base Substances 0.000 description 27
- 239000002299 complementary DNA Substances 0.000 description 27
- 230000020477 pH reduction Effects 0.000 description 27
- 150000001299 aldehydes Chemical class 0.000 description 26
- 230000003248 secreting effect Effects 0.000 description 26
- 108010062580 Concanavalin A Proteins 0.000 description 25
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 24
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 24
- 239000001257 hydrogen Substances 0.000 description 24
- 229910052739 hydrogen Inorganic materials 0.000 description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
- 238000002493 microarray Methods 0.000 description 22
- 238000000926 separation method Methods 0.000 description 22
- 108020004459 Small interfering RNA Proteins 0.000 description 21
- 238000009396 hybridization Methods 0.000 description 21
- 210000004986 primary T-cell Anatomy 0.000 description 21
- 239000004971 Cross linker Substances 0.000 description 20
- 230000001464 adherent effect Effects 0.000 description 20
- -1 azido sugars Chemical class 0.000 description 20
- 238000001514 detection method Methods 0.000 description 20
- 108020004999 messenger RNA Proteins 0.000 description 20
- 238000012544 monitoring process Methods 0.000 description 20
- 238000000059 patterning Methods 0.000 description 20
- 239000000872 buffer Substances 0.000 description 19
- 238000010804 cDNA synthesis Methods 0.000 description 19
- 238000005859 coupling reaction Methods 0.000 description 19
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 230000008878 coupling Effects 0.000 description 18
- 238000010168 coupling process Methods 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 238000005516 engineering process Methods 0.000 description 18
- 239000000499 gel Substances 0.000 description 18
- 230000003993 interaction Effects 0.000 description 18
- 230000002503 metabolic effect Effects 0.000 description 18
- 125000003729 nucleotide group Chemical group 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 17
- 108020004635 Complementary DNA Proteins 0.000 description 17
- 241000196324 Embryophyta Species 0.000 description 17
- 230000008901 benefit Effects 0.000 description 17
- 230000001588 bifunctional effect Effects 0.000 description 17
- 150000001720 carbohydrates Chemical class 0.000 description 17
- 239000004205 dimethyl polysiloxane Substances 0.000 description 17
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 17
- 239000003446 ligand Substances 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 17
- 238000003752 polymerase chain reaction Methods 0.000 description 17
- 230000004044 response Effects 0.000 description 17
- 108020004463 18S ribosomal RNA Proteins 0.000 description 16
- 229920002477 rna polymer Polymers 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 206010028980 Neoplasm Diseases 0.000 description 15
- 210000001744 T-lymphocyte Anatomy 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 235000014633 carbohydrates Nutrition 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 230000009257 reactivity Effects 0.000 description 15
- 210000004102 animal cell Anatomy 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 14
- 230000001413 cellular effect Effects 0.000 description 14
- 230000021615 conjugation Effects 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 239000001301 oxygen Substances 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
- 238000003757 reverse transcription PCR Methods 0.000 description 14
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 230000004069 differentiation Effects 0.000 description 13
- 239000010931 gold Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 210000003098 myoblast Anatomy 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 150000008163 sugars Chemical class 0.000 description 13
- 241000195493 Cryptophyta Species 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000013459 approach Methods 0.000 description 12
- 210000000170 cell membrane Anatomy 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 12
- 229910052737 gold Inorganic materials 0.000 description 12
- 150000002576 ketones Chemical class 0.000 description 12
- 239000011159 matrix material Substances 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 108091093088 Amplicon Proteins 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- 229910052782 aluminium Inorganic materials 0.000 description 11
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 11
- 239000000090 biomarker Substances 0.000 description 11
- 238000005251 capillar electrophoresis Methods 0.000 description 11
- 230000021164 cell adhesion Effects 0.000 description 11
- HTXDPTMKBJXEOW-UHFFFAOYSA-N dioxoiridium Chemical compound O=[Ir]=O HTXDPTMKBJXEOW-UHFFFAOYSA-N 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 230000012010 growth Effects 0.000 description 11
- 229910000457 iridium oxide Inorganic materials 0.000 description 11
- 210000004379 membrane Anatomy 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 235000012431 wafers Nutrition 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 239000007853 buffer solution Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000030279 gene silencing Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 230000002441 reversible effect Effects 0.000 description 10
- 230000035945 sensitivity Effects 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 9
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 9
- 238000002372 labelling Methods 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 238000000206 photolithography Methods 0.000 description 9
- 230000000243 photosynthetic effect Effects 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 238000010839 reverse transcription Methods 0.000 description 9
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 239000002699 waste material Substances 0.000 description 9
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 230000003321 amplification Effects 0.000 description 8
- 239000012491 analyte Substances 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 210000002919 epithelial cell Anatomy 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 238000003384 imaging method Methods 0.000 description 8
- 230000004060 metabolic process Effects 0.000 description 8
- 230000000813 microbial effect Effects 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 238000005691 oxidative coupling reaction Methods 0.000 description 8
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 8
- 230000029553 photosynthesis Effects 0.000 description 8
- 238000010672 photosynthesis Methods 0.000 description 8
- 125000003396 thiol group Chemical group [H]S* 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 7
- 229930182555 Penicillin Natural products 0.000 description 7
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 7
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 230000024245 cell differentiation Effects 0.000 description 7
- 239000006285 cell suspension Substances 0.000 description 7
- 230000003833 cell viability Effects 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 238000003795 desorption Methods 0.000 description 7
- 238000002296 dynamic light scattering Methods 0.000 description 7
- 230000005611 electricity Effects 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 238000010195 expression analysis Methods 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 102000006495 integrins Human genes 0.000 description 7
- 108010044426 integrins Proteins 0.000 description 7
- 238000004949 mass spectrometry Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 235000015097 nutrients Nutrition 0.000 description 7
- 239000007800 oxidant agent Substances 0.000 description 7
- 229940049954 penicillin Drugs 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 150000003384 small molecules Chemical class 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229960005322 streptomycin Drugs 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- 230000008836 DNA modification Effects 0.000 description 6
- 230000004568 DNA-binding Effects 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 101001024703 Homo sapiens Nck-associated protein 5 Proteins 0.000 description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
- 102100036946 Nck-associated protein 5 Human genes 0.000 description 6
- 108091093037 Peptide nucleic acid Proteins 0.000 description 6
- 241000192584 Synechocystis Species 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 238000003491 array Methods 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 238000000151 deposition Methods 0.000 description 6
- 230000006539 extracellular acidification Effects 0.000 description 6
- 238000012226 gene silencing method Methods 0.000 description 6
- 150000007857 hydrazones Chemical class 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 229930182817 methionine Natural products 0.000 description 6
- 210000003097 mucus Anatomy 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 238000007639 printing Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000006268 reductive amination reaction Methods 0.000 description 6
- 229940080817 rotenone Drugs 0.000 description 6
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000001685 thyroid gland Anatomy 0.000 description 6
- 239000012581 transferrin Substances 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 241000192700 Cyanobacteria Species 0.000 description 5
- 238000000018 DNA microarray Methods 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000004856 Lectins Human genes 0.000 description 5
- 108090001090 Lectins Proteins 0.000 description 5
- 241000872931 Myoporum sandwicense Species 0.000 description 5
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000005352 borofloat Substances 0.000 description 5
- 238000004422 calculation algorithm Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 238000006073 displacement reaction Methods 0.000 description 5
- 238000001962 electrophoresis Methods 0.000 description 5
- 230000003325 follicular Effects 0.000 description 5
- 150000004676 glycans Chemical class 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000010354 integration Effects 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000002523 lectin Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 210000001916 photosynthetic cell Anatomy 0.000 description 5
- 229920001282 polysaccharide Polymers 0.000 description 5
- 239000005017 polysaccharide Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000005382 thermal cycling Methods 0.000 description 5
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical group NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 241000589149 Azotobacter vinelandii Species 0.000 description 4
- 101710132601 Capsid protein Proteins 0.000 description 4
- 101710094648 Coat protein Proteins 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
- 108091093094 Glycol nucleic acid Proteins 0.000 description 4
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- 101710125418 Major capsid protein Proteins 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 4
- 241000713869 Moloney murine leukemia virus Species 0.000 description 4
- 101710141454 Nucleoprotein Proteins 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 101710083689 Probable capsid protein Proteins 0.000 description 4
- 229910052581 Si3N4 Inorganic materials 0.000 description 4
- 241000192593 Synechocystis sp. PCC 6803 Species 0.000 description 4
- 102000004338 Transferrin Human genes 0.000 description 4
- 108090000901 Transferrin Proteins 0.000 description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 239000003431 cross linking reagent Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 229930182830 galactose Natural products 0.000 description 4
- 238000002523 gelfiltration Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 238000011331 genomic analysis Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 210000004209 hair Anatomy 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 150000002466 imines Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 230000004073 interleukin-2 production Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 4
- 238000002715 modification method Methods 0.000 description 4
- 210000000107 myocyte Anatomy 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- 229920000052 poly(p-xylylene) Polymers 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 210000000106 sweat gland Anatomy 0.000 description 4
- 230000017423 tissue regeneration Effects 0.000 description 4
- 238000004627 transmission electron microscopy Methods 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- 238000012800 visualization Methods 0.000 description 4
- AFNOHTDETQTADW-YLRIPHBZSA-N 2-azido-n-[(3s,4r,5s,6r)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound OC[C@H]1OC(O)[C@@H](NC(=O)CN=[N+]=[N-])[C@@H](O)[C@@H]1O AFNOHTDETQTADW-YLRIPHBZSA-N 0.000 description 3
- CMUHFUGDYMFHEI-QMMMGPOBSA-N 4-amino-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N)C=C1 CMUHFUGDYMFHEI-QMMMGPOBSA-N 0.000 description 3
- IPJDHSYCSQAODE-UHFFFAOYSA-N 5-chloromethylfluorescein diacetate Chemical compound O1C(=O)C2=CC(CCl)=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 IPJDHSYCSQAODE-UHFFFAOYSA-N 0.000 description 3
- 239000012103 Alexa Fluor 488 Substances 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 239000002028 Biomass Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 241000195628 Chlorophyta Species 0.000 description 3
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 108091008102 DNA aptamers Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010040476 FITC-annexin A5 Proteins 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- 101150112014 Gapdh gene Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102100039813 Inactive tyrosine-protein kinase 7 Human genes 0.000 description 3
- 101710099452 Inactive tyrosine-protein kinase 7 Proteins 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- 229920000557 Nafion® Polymers 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- 239000012979 RPMI medium Substances 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- HGMISDAXLUIXKM-LIADDWGISA-N [(2r,3s,4r,5s)-3,4,6-triacetyloxy-5-[(2-azidoacetyl)amino]oxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1OC(OC(C)=O)[C@@H](NC(=O)CN=[N+]=[N-])[C@@H](OC(C)=O)[C@@H]1OC(C)=O HGMISDAXLUIXKM-LIADDWGISA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 125000003172 aldehyde group Chemical group 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium peroxydisulfate Substances [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 3
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 210000000270 basal cell Anatomy 0.000 description 3
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 3
- 238000012742 biochemical analysis Methods 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 229910052799 carbon Chemical group 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000002458 cell surface marker Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 238000002059 diagnostic imaging Methods 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 238000000132 electrospray ionisation Methods 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 210000004907 gland Anatomy 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 210000002175 goblet cell Anatomy 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 244000059217 heterotrophic organism Species 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000005265 lung cell Anatomy 0.000 description 3
- 150000002772 monosaccharides Chemical class 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000000849 parathyroid Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000001817 pituitary effect Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 102000054765 polymorphisms of proteins Human genes 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 210000004918 root sheath Anatomy 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 210000002105 tongue Anatomy 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 2
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 2
- OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 2
- RDFMDVXONNIGBC-UHFFFAOYSA-N 2-aminoheptanoic acid Chemical compound CCCCCC(N)C(O)=O RDFMDVXONNIGBC-UHFFFAOYSA-N 0.000 description 2
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 108090000672 Annexin A5 Proteins 0.000 description 2
- 102000004121 Annexin A5 Human genes 0.000 description 2
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 2
- 241000099686 Azotobacter sp. Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 240000008996 Empetrum rubrum Species 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
- 244000281247 Ribes rubrum Species 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 108020004422 Riboswitch Proteins 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 108091033762 Smart ligand Proteins 0.000 description 2
- 102100038803 Somatotropin Human genes 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 241000192581 Synechocystis sp. Species 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 108091046915 Threose nucleic acid Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- YJZATOSJMRIRIW-UHFFFAOYSA-N [Ir]=O Chemical class [Ir]=O YJZATOSJMRIRIW-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 210000004504 adult stem cell Anatomy 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 2
- 210000002255 anal canal Anatomy 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 210000000233 bronchiolar non-ciliated Anatomy 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000012578 cell culture reagent Substances 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 210000003737 chromaffin cell Anatomy 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 239000012881 co-culture medium Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 239000005289 controlled pore glass Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000000840 electrochemical analysis Methods 0.000 description 2
- 238000002848 electrochemical method Methods 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 230000002327 eosinophilic effect Effects 0.000 description 2
- 150000002118 epoxides Chemical class 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 238000005530 etching Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 238000003197 gene knockdown Methods 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 210000001822 immobilized cell Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000002332 leydig cell Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000002596 lutein cell Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000000696 magnetic material Substances 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 210000003593 megakaryocyte Anatomy 0.000 description 2
- 210000003584 mesangial cell Anatomy 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005787 mitochondrial ATP synthesis coupled electron transport Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 230000004660 morphological change Effects 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- ZNALDVNNEBOGGN-UHFFFAOYSA-N n-(2,5-dioxopyrrol-1-yl)propanamide Chemical compound CCC(=O)NN1C(=O)C=CC1=O ZNALDVNNEBOGGN-UHFFFAOYSA-N 0.000 description 2
- 239000002090 nanochannel Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 210000000581 natural killer T-cell Anatomy 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 210000001719 neurosecretory cell Anatomy 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 108091008104 nucleic acid aptamers Proteins 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 229920002120 photoresistant polymer Polymers 0.000 description 2
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- 238000012342 propidium iodide staining Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 239000010453 quartz Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000985 reactive dye Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000001995 reticulocyte Anatomy 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 210000003079 salivary gland Anatomy 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 210000001625 seminal vesicle Anatomy 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 210000000717 sertoli cell Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000006557 surface reaction Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 201000010653 vesiculitis Diseases 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- GNYFRUPBSKTCIC-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 5-[4-(diethylamino)anilino]-5-oxopentanoate Chemical compound C1=CC(N(CC)CC)=CC=C1NC(=O)CCCC(=O)ON1C(=O)CCC1=O GNYFRUPBSKTCIC-UHFFFAOYSA-N 0.000 description 1
- BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 1
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- VEVRNHHLCPGNDU-MUGJNUQGSA-N (2s)-2-amino-5-[1-[(5s)-5-amino-5-carboxypentyl]-3,5-bis[(3s)-3-amino-3-carboxypropyl]pyridin-1-ium-4-yl]pentanoate Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(CC[C@H](N)C(O)=O)=C(CCC[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 VEVRNHHLCPGNDU-MUGJNUQGSA-N 0.000 description 1
- XJPHGGXFBWOHFL-QMMMGPOBSA-N (2s)-2-hydrazinyl-3-(4-hydroxyphenyl)propanoic acid Chemical compound NN[C@H](C(O)=O)CC1=CC=C(O)C=C1 XJPHGGXFBWOHFL-QMMMGPOBSA-N 0.000 description 1
- QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 1
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000000424 1,2-diol group Chemical group 0.000 description 1
- 150000000180 1,2-diols Chemical class 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 description 1
- ABQQPHFTJYCSIA-UHFFFAOYSA-N 2,3-diethylbenzene-1,4-diamine Chemical compound CCC1=C(N)C=CC(N)=C1CC ABQQPHFTJYCSIA-UHFFFAOYSA-N 0.000 description 1
- AHLFJIALFLSDAQ-UHFFFAOYSA-N 2-(pentylazaniumyl)acetate Chemical compound CCCCCNCC(O)=O AHLFJIALFLSDAQ-UHFFFAOYSA-N 0.000 description 1
- TXHAHOVNFDVCCC-UHFFFAOYSA-N 2-(tert-butylazaniumyl)acetate Chemical compound CC(C)(C)NCC(O)=O TXHAHOVNFDVCCC-UHFFFAOYSA-N 0.000 description 1
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-CBPJZXOFSA-N 2-amino-2-deoxy-D-mannopyranose Chemical compound N[C@@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-CBPJZXOFSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- ZSPZGQROIGAVRR-UHFFFAOYSA-N 2-trimethoxysilylpropanal Chemical group CO[Si](OC)(OC)C(C)C=O ZSPZGQROIGAVRR-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 1
- XABCFXXGZPWJQP-UHFFFAOYSA-N 3-aminoadipic acid Chemical compound OC(=O)CC(N)CCC(O)=O XABCFXXGZPWJQP-UHFFFAOYSA-N 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- VGRWVABESTUTTB-UHFFFAOYSA-N 5-[4-(diethylamino)anilino]-5-oxopentanoic acid Chemical compound CCN(CC)C1=CC=C(NC(=O)CCCC(O)=O)C=C1 VGRWVABESTUTTB-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 1
- 241000349731 Afzelia bipindensis Species 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091029845 Aminoallyl nucleotide Proteins 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 238000010207 Bayesian analysis Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 240000002791 Brassica napus Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241001161843 Chandra Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000004155 Chlorine dioxide Substances 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 101800000414 Corticotropin Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000009025 Endorphins Human genes 0.000 description 1
- 108010049140 Endorphins Proteins 0.000 description 1
- 241000709744 Enterobacterio phage MS2 Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 101100175482 Glycine max CG-3 gene Proteins 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 241000056817 Halosimplex rubrum Species 0.000 description 1
- 229920002488 Hemicellulose Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010020056 Hydrogenase Proteins 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 241000221089 Jatropha Species 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- JUQLUIFNNFIIKC-YFKPBYRVSA-N L-2-aminopimelic acid Chemical compound OC(=O)[C@@H](N)CCCCC(O)=O JUQLUIFNNFIIKC-YFKPBYRVSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108091036060 Linker DNA Proteins 0.000 description 1
- 102000003752 Lipocalin 1 Human genes 0.000 description 1
- 108010057281 Lipocalin 1 Proteins 0.000 description 1
- 101500021084 Locusta migratoria 5 kDa peptide Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 1
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 1
- 206010027145 Melanocytic naevus Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101001043827 Mus musculus Interleukin-2 Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-OZRXBMAMSA-N N-acetyl-beta-D-mannosamine Chemical compound CC(=O)N[C@@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-OZRXBMAMSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- OLNLSTNFRUFTLM-UHFFFAOYSA-N N-ethylasparagine Chemical compound CCNC(C(O)=O)CC(N)=O OLNLSTNFRUFTLM-UHFFFAOYSA-N 0.000 description 1
- YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
- 108010065338 N-ethylglycine Proteins 0.000 description 1
- CNIUEVQJABPUIJ-QMMMGPOBSA-N N-hydroxytyrosine Chemical compound ON[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNIUEVQJABPUIJ-QMMMGPOBSA-N 0.000 description 1
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 1
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 102400000050 Oxytocin Human genes 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 108010079855 Peptide Aptamers Proteins 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 108010086019 Secretin Proteins 0.000 description 1
- 102100037505 Secretin Human genes 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 241000863430 Shewanella Species 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101710136739 Teichoic acid poly(glycerol phosphate) polymerase Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000010062 adhesion mechanism Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000002154 agricultural waste Substances 0.000 description 1
- 210000005058 airway cell Anatomy 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000005303 alkyl halide derivatives Chemical class 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- VAZSKTXWXKYQJF-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)OOS([O-])=O VAZSKTXWXKYQJF-UHFFFAOYSA-N 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000004396 apud cell Anatomy 0.000 description 1
- QZPSXPBJTPJTSZ-UHFFFAOYSA-N aqua regia Chemical compound Cl.O[N+]([O-])=O QZPSXPBJTPJTSZ-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000001651 autotrophic effect Effects 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 210000004082 barrier epithelial cell Anatomy 0.000 description 1
- 210000002947 bartholin's gland Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000000465 brunner gland Anatomy 0.000 description 1
- 238000011095 buffer preparation Methods 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 210000002533 bulbourethral gland Anatomy 0.000 description 1
- 239000013590 bulk material Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- VULFYOXOVPJBLV-UHFFFAOYSA-N carbonochloridic acid;1-hydroxypyrrolidine-2,5-dione Chemical compound OC(Cl)=O.ON1C(=O)CCC1=O VULFYOXOVPJBLV-UHFFFAOYSA-N 0.000 description 1
- 150000003857 carboxamides Chemical group 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000007444 cell Immobilization Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000008568 cell cell communication Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000005229 chemical vapour deposition Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 235000019398 chlorine dioxide Nutrition 0.000 description 1
- 229910001902 chlorine oxide Inorganic materials 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- ASARMUCNOOHMLO-WLORSUFZSA-L cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2s)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O ASARMUCNOOHMLO-WLORSUFZSA-L 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000006854 communication Effects 0.000 description 1
- 238000012733 comparative method Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000005112 continuous flow technique Methods 0.000 description 1
- 210000000555 contractile cell Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 239000007819 coupling partner Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 150000004845 diazirines Chemical class 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 150000001989 diazonium salts Chemical group 0.000 description 1
- 238000004720 dielectrophoresis Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005370 electroosmosis Methods 0.000 description 1
- 238000009713 electroplating Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 210000005168 endometrial cell Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000004188 enterochromaffin-like cell Anatomy 0.000 description 1
- 210000003158 enteroendocrine cell Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000003426 epidermal langerhans cell Anatomy 0.000 description 1
- 208000037828 epithelial carcinoma Diseases 0.000 description 1
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000010429 evolutionary process Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 210000001813 extracellular matrix secreting cell Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 238000009313 farming Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000004904 fingernail bed Anatomy 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000001298 force spectroscopy Methods 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 210000004565 granule cell Anatomy 0.000 description 1
- 210000003772 granulosa lutein cell Anatomy 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 125000005179 haloacetyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 1
- 208000002557 hidradenitis Diseases 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 230000005571 horizontal transmission Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- RGXCTRIQQODGIZ-UHFFFAOYSA-O isodesmosine Chemical compound OC(=O)C(N)CCCC[N+]1=CC(CCC(N)C(O)=O)=CC(CCC(N)C(O)=O)=C1CCCC(N)C(O)=O RGXCTRIQQODGIZ-UHFFFAOYSA-O 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 238000012177 large-scale sequencing Methods 0.000 description 1
- 238000000370 laser capture micro-dissection Methods 0.000 description 1
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 1
- 210000003644 lens cell Anatomy 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000001459 lithography Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000007309 lysosomal acidification Effects 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 150000002703 mannose derivatives Chemical class 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical class Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000007826 nucleic acid assay Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 210000001915 nurse cell Anatomy 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 238000002966 oligonucleotide array Methods 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 238000012576 optical tweezer Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002488 outer root sheath cell Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000000277 pancreatic duct Anatomy 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 210000000557 podocyte Anatomy 0.000 description 1
- 238000012123 point-of-care testing Methods 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 239000005518 polymer electrolyte Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001115 scanning electrochemical microscopy Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 229960002101 secretin Drugs 0.000 description 1
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 239000004054 semiconductor nanocrystal Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000003728 serous cell Anatomy 0.000 description 1
- 210000002107 sheath cell Anatomy 0.000 description 1
- 230000006807 siRNA silencing Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000352 storage cell Anatomy 0.000 description 1
- 210000000710 stratified squamous epithelial cell Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 208000025889 stromal keratitis Diseases 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000034005 thiol-disulfide exchange Effects 0.000 description 1
- YSMODUONRAFBET-WHFBIAKZSA-N threo-5-hydroxy-L-lysine Chemical compound NC[C@@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-WHFBIAKZSA-N 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 238000011222 transcriptome analysis Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 238000007740 vapor deposition Methods 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 210000001849 von ebner gland Anatomy 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0006—Modification of the membrane of cells, e.g. cell decoration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
Description
本出願は、全ての目的のために全体として本明細書に援用される、2009年4月8日に出願された米国出願第61/167,748号、及び2009年9月16日に出願された米国出願第61/243,123号の優先権を主張する。
本研究は、米国エネルギー省によって承認され、エネルギー省、及び科学局、基礎エネルギー科学局のナノスケールサイエンスエンジニアリング及びテクノロジー(NSET)プログラムによって支援された助成金番号DE−AC02−05CH11231により、国立衛生研究所によって承認されたHG003329及びR01GM072700により、並びに国立衛生研究所の分子生物物理学訓練助成金T32GM08295により、政府支援に基づいてなされた。合衆国政府は本発明に一定の権利を有する。
該当なし
I.一般
本発明は、代謝工学を必要とせずに、細胞表面上の天然の官能基を介して、DNAを細胞に共有的に連結させることによって調製される細胞−DNAコンジュゲートの最初の例を提供する。細胞壁を持たない哺乳動物細胞及び他の細胞について、DNAは、リジンアミンなどの、細胞表面のアミノ酸に直接共有結合される。細胞壁を持たない植物細胞及び他の細胞について、細胞の表面上の糖類は、アルデヒド又はケトンを形成するように、例えば酸化によって最初に修飾され、次にDNAで修飾される。
「細胞」は、生命の基本的な機能的単位を意味し、原核細胞及び真核細胞の両方を含む。細胞は、核又は核様体を有する内部、及び細胞膜(細胞表面)によって特徴付けられる。細胞はまた細胞壁を有してもよい。細胞壁を持たない細胞は、真核細胞、哺乳動物細胞、及び幹細胞を含む。細胞壁を有する原核細胞及び植物細胞を含む。他の細胞は、本発明において有用である。
1)アラニン(A)、グリシン(G);
2)アスパラギン酸(D)、グルタミン酸(E);
3)アスパラギン(N)、グルタミン(Q);
4)アルギニン(R)、リジン(K);
5)イソロイシン(I)、ロイシン(L)、メチオニン(M)、バリン(V);
6)フェニルアラニン(F)、チロシン(Y)、トリプトファン(W);
7)セリン(S)、スレオニン(T);及び
8)システイン(C)、メチオニン(M)
(例えば、Creighton,Proteins(1984)参照)。
本発明は、細胞−DNAコンジュゲート及びコンジュゲートを製造するための方法を提供する。
本発明は、核酸部分と、細胞壁を持たない細胞とのコンジュゲートを提供する。コンジュゲートは、細胞表面上に天然の官能基を介して細胞表面に核酸部分を共有的に連結させることによって形成される。本発明のコンジュゲートに使用される細胞は任意の細胞であってもよく、核酸部分をコンジュゲートするために官能基を導入する代謝工学を必要としない。
−アミン反応性+スルフヒドリル反応性架橋剤。
−カルボニル反応性+スルフヒドリル反応性架橋剤。
−アミン反応性+光反応性架橋剤。
−スルフヒドリル反応性+光反応性架橋剤。
−カルボニル反応性+光反応性架橋剤。
−カルボン酸塩反応性+光反応性架橋剤。
−アルギニン反応性+光反応性架橋剤。
1.アミノ反応性:アミン(NH2)含有分子への架橋剤カップリング。
2.チオール反応性:スルフヒドリル(SH)含有分子への架橋剤カップリング。
3.カルボン酸塩反応性:カルボン酸(COOH)含有分子への架橋剤カップリング。
4.ヒドロキシル反応性:ヒドロキシル(−OH)含有分子への架橋剤カップリング。
5.アルデヒド及びケトン反応性:アルデヒド(−CHO)又はケトン(R2CO)含有分子への架橋剤カップリング。
6.活性水素反応性。
7.光反応性。
1.イソチオシアネート、イソシアネート、アシルアジド、NHSエステル、スルホニルクロリド、アルデヒド及びグリオキサル、エポキシド及びオキシラン、カーボネート、アリール化剤、イミドエステル、カルボジイミド、無水物、アルキン。
2.ハロアセチル及びハロゲン化アルキル誘導体、マレイミド、アジリジン、アクリロイル誘導体、アリール化剤、チオールジスルフィド交換試薬。
3.ジアゾアルカン及びジアゾアセチル化合物、例えば、カルボニルジイミダゾール及びカルボジイミド。
4.エポキシド及びオキシラン、カルボニルジイミダゾール、過ヨウ素酸塩を用いた酸化、N,N’−ジスクシンイミジルカーボネート又はN−ヒドロキシスクシンイミドクロロホルメート、酵素的酸化、アルキルハロゲン、イソシアネート。
5.シッフ塩基形成又は還元アミノ化のためのヒドラジン誘導体。
6.マンニッヒ縮合及びヨウ素化反応のためのジアゾニウム誘導体。
7.アリールアジド及びハロゲン化アリールアジド、ベンゾフェノン、ジアゾ化合物、ジアジリン誘導体。
また、本発明は、核酸部分と細胞壁を有する細胞とのコンジュゲート、及びそれを製造する方法を提供する。いくつかの態様では、本発明は、細胞壁を有する細胞と核酸部分とのコンジュゲートを提供し、ここで、核酸部分は細胞に共有結合される。他の態様では、核酸部分は、細胞表面に共有結合される。
また、本発明は、本発明のコンジュゲートを含む基質表面及びデバイスを提供する。いくつかの態様では、本発明は、第1の核酸部分に共有結合される天然の官能基を含む細胞表面を有する細胞を含むデバイスを提供する。また、このデバイスは、第1の核酸部分に相補的な第2の核酸部分を含む基質表面を含み、それにより、細胞は、第1及び第2の核酸部分の核酸二重鎖の形成を介して基質表面に結合される。
本発明はまた、本発明の核酸−細胞コンジュゲートの形成に適した活性化された核酸部分、及び相補的核酸部分を有する基質表面を有するキットを提供する。いくつかの態様では、本発明は、細胞表面の天然の官能基への供給結合に適した活性化された核酸部分、及び該活性化された核酸部分に相補的な核酸部分を含む基質表面を提供する。活性化された核酸部分は粉末であってもよく、又は溶液中にあってもよい。また、キットは当業者に知られている緩衝溶液、及び核酸−細胞コンジュゲートを形成し、次に、該核酸−細胞コンジュゲートを、基質表面上の核酸部分を介して基質表面に結合させるための他の溶液を含んでもよい。
実施例1.リジン天然官能基を介した細胞壁を持たない細胞へのDNAのコンジュゲーション
全ての細胞培養試薬は、特記がなければ、Gibco/Invitrogen Corp(Carlsbad,CA)から購入した。細胞培養は、標準的な技術を用いて行われた。Jurkat細胞は、10%(v/v)牛胎仔血清(FBS,Hyclone)及び1%ペニシリン/ストレプトマイシン(P/S,Sigma)を捕捉したRPMI培地1640中でT−25培養フラスコ(Corning,米国)において増殖させた。MCF−7細胞は、1%非必須アミノ酸及び10%牛胎仔血清+1%ペニシリン/ストレプトマイシンを捕捉したDMEM中で増殖させた。MDA−MB−231細胞は、MCF−7細胞と同じ条件であるが、非必須アミノ酸なしで増殖させた。
C1:5’−GTA ACG ATC CAG CTG TCA CT−3’(配列番号1)
M1:5’−AGT GAC AGC TGG ATC GTT AC−3’(配列番号2)
C2:5’−TC A TAC GAC TCA CTC TAG GG−3’(配列番号3)
M2:5’−CCC TAG AGT GAG TCG TAT GA−3’(配列番号4)
C3:5’−ACT GAC TGA CTG ACT GAC TG−3’(配列番号5)
M3:5’−CAG TCA GTC AGT CAG TCA GT−3’(配列番号6)
DNAは、以下の手法によって、EDCカップリング化学を用いて細胞にコンジュゲートされた:
1.5ミクロンの細胞を採取し、10mLのPBSで2回洗浄する。
2.0.366gのEDCを19.06mLのPBSに溶解させる。
3.0.452gのNHSをEDC溶液に添加する。
4.pHが7近辺であることを確認する(通常はそうである)。
5.このEDC/NHS溶液を1mL採取し、200μLの80μMアミン−ssDNA(1×SSC中)を添加する。
6.室温で30分〜1時間インキュベートする。
7.10mLの1%FBS/PBSで3回洗浄する。
8.50〜100μLの1%FBS/PBSに再懸濁させ、スライドに載せるために準備をする。
細胞壁を持つ細胞上での表面曝露されたジオール類(リポ多糖、リポタイコ酸など)の酸化。1mLのダルベッコリン酸緩衝生理食塩水(DPBS)中の細胞(105〜107個)を遠心分離を用いてリンスする。DPBS中の0.5〜5mMのNaIO4の2mLに細胞を懸濁し、20分間、軌道振とうしながら37℃に置いた。低濃度の過ヨウ素酸塩は、藻類及び酵母などの原核生物には必要である。DPBS中の1mLの0.1Mグルコースを用いて過ヨウ素酸塩を中和する。細胞を遠心分離して沈殿させ、2×1mLのDPBS、1×1mL pH6のMOPS緩衝液で洗浄する(下記参照)。
DNA鎖の細胞への結合、及びDNAをプリントした表面へのそれらの固定のための一般的なプロトコールは以下の通りであった:修飾の直前に、5×106個のJurkat細胞の試料は、PBSを用いて3回洗浄し、培地からいずれのタンパク質を除去した。最終リンス後、追加のPSを添加し、体積を5mLにした(1×106細胞/mL)。次に、細胞懸濁物は、30μLの5’−チオールssDNA(C2配列)から合成及び精製された1mLのNHS−DNA(11.7μM)溶液と反応した。混合物は、室温にて30分間反応させ、次に1%FBS含有PBSを用いて3回洗浄した。その後、細胞は、1%FBS含有PBSの0.5mLに再懸濁された。
微小デバイスは、代謝分析のためおpH感受性微小電極のアレイ上で単一細胞のDNAバーコード指向された捕捉用に開発された。細胞は、膜結合の一本鎖DNAを用いて修飾され、特定の単一細胞捕捉は、微小流体チャネル内の酸化イリジウムpH微小電極のセンサー領域に結合された捕捉鎖によって指向される。この二機能性微小電極アレイは、pHモニタリング、並びに初代T細胞及びJurkatTリンパ球の分化について実証される。単一のJurkat細胞は、11ミリpH/分の細胞外酸性速度を示し、一方、初代T細胞はたった2ミリpH/分を示した。このシステムを用いて、特異的に非接着細胞を捕捉し、代謝特性の変化に基づく異種案産物における視覚的に同じ健常な細胞と癌性細胞との間を区別することができる。本明細書に示されている二機能性微小電極は、本発明の組成を用いて作製されたデバイスが、選択的に細胞を捕捉し、それらの電気的及び代謝的活性を測定する能力をどのようにして持つのかを示す。DNA−バーコード捕捉を用いて、接着細胞と自然な非接着細胞とが同じデバイス上で研究され得る。さらに、このように捕捉された細胞は活性化されない。アレイフォーマットは、混合物から細胞間を直接区別でき、単一細胞特性における変化、及びその細胞が全体にどのように寄与するかを示す。制御された単一細胞の電気化学的測定は、細胞活性の多重な細胞内分析を可能にする名のスケールの細胞接触面を用いることを指摘する。
単一細胞分析は、同系細胞集団内で遺伝子発現の変化を理解するための強力なアプローチである。マイクロアレイ及び遺伝子発現の連続分析などの伝統的な遺伝子発現分析は、単一細胞レベルでの変化、及び大多数の細胞のアンサンブル平均挙動に関する単なる記録を分析するには十分感受性でない。最近、多種の高感度であり、特殊化された技術が、単一細胞における遺伝子発現を探査するために開発されている。これらのアプローチの多くはリアルタイムモニタリングの利点を提供するが、必要されるプロトコールは困難であり、多くの場合、細胞操作を必要とし、限定された多重化能力を有する。
糖質上のアルデヒド又はケトンを介して非動物細胞へのオリゴヌクレオチド結合に適用される本発明の原理を用いて、水素生成効率を研究及び最適化することができる。デバイスに対するオリゴヌクレオチドの捕捉及び結合により、チップ上でパターン化された細胞及び酵素の作製を可能にする。システムにおいて、電気へん水素ガスの変換は、水素生成を測定する。電流生成を介した直接的な水素生成の測定は、従来の測定と比較して、水素生成に対する潜在的に高い感受性のために有利である(培養の上部空間のGS表示を参照)。このような研究及び作動に対する本発明の利点には、デバイス上の細胞の正確な配置を伴う結合及び制御インプリシットを含み、次に、燃料電池は再利用可能であり、また燃料及びカーボンエネルギーの利用において高効率である。例えば、自立型燃料電池デバイスは、異なる光合成電池のパターン化された層を用いて構築することができ、この場合、電池は、太陽スペクトルの重ならない部分において太陽光を吸収し、さらに、隣接層の光合成電池によって作られたバイオマスを供給し、利用する窒素固定生物の代替層(単数又は複数)を組み込む。消耗した場合、オリゴヌクレオチドハイブリダイゼーションによって結合された細胞を有する燃料電池は加熱され、オリゴヌクレオチドは脱ハイブリダイズし、死細胞は洗い出される。表面は、デバイス表面上の相補的オリゴヌクレオチドに再度結合する新鮮な修飾された細胞を用いて全体がリンスされる。しかしながら、ゾルゲル包埋された細胞を有するゾルゲルデバイスは廃棄され、同じように再使用することはできないが、この代謝回転はそれらの標的とされた応答に適している場合がある。
力支配の細胞−細胞間接着は、多くの生物学的プロセスに極めて重要であり、細胞分化、組織成長、腫瘍形成、及び脊椎動物の免疫応答の適切な機能化が挙げられる。これらの相互作用の強度は、典型的には、吸入マイクロピペットなどの力測定を可能にするプローブへの単一の生細胞の結合を介して特徴付けられる。ごく細菌、光学ピンセットが単一細胞の捕捉、及び高精度でこれらの力の測定に適用されているが、この技術は、ピコニュートンレンジでの力を適用することに限定される。原子間力顕微鏡(AFM)は、これらの方法に魅力的に代わるものを提供し、それは、ピコニュートンからナノニュートンで力を定量することができるためであり、この技術は、単一の生細胞の機械的特性を測定し、単一細胞レベルでの接着力を研究するために実際に使用されている。いくつかの基本的な接着測定は、細胞表面上で糖質部分に結合するフィブロネクチン又はレクチンを用いてAFMカンチレバーを被覆することによって達成されているが、特に、後者の場合には、細胞結合分子それ自体が、評価される細胞統制に影響を及ぼし得るある程度の細胞毒性を有することが報告されている。このようにして、これらの研究は、細胞受容体−リガンド相互作用の測定についてAFMの用途を強調するが、拡大された一連のカンチレバー結合法は、幅広く変化する時間スケールに対して、細胞−細胞間相互作用の研究に必要とされる。
A:5’−TCA TAC GAC TCA CTC TAG GG−3’(配列番号23)
A:5’−CCC TAG AGT GAG TCG TAT GA−3’(配列番号24)
多価の標的送達ビヒクルのためのウイルスキャプシドの修飾。多価であり、標的とされた送達ビヒクルは、薬物投与及び診断画像のために大きな保証を与える。多数のコア足場、例えば、ポリマー、デンドリマー、無機ナノ粒子、及びリポソームは、これらの応用における顕著な成功をもって使用されてきた。生体分子に基づくベクターに関して、操作された熱ショックケージ及びウイルスキャプシドはまた、それらの内側に薬物分子を収納するように開発されてきた。これらの担体タイプの各々について、非常に重要な検討事項は、担体と標的とされた組織タイプの選択的関連性を可能にする受容体結合グループの設置である。この目的のための最も共通した分子ストラテジーは、葉酸、コバラミン、糖質、ペプチド及び抗体、並びに核酸アプタマーを伴っている。これらの分子の豊富な化学的多様性は、組成物を変化させるための足場に各々の複数コピーを付着させる希望に加えて、見事に官能化された基の寛容、及び生理学的条件下で進められる化学的反応を要求する。
A:5’−TCATACGACTCACTCTAGGGA−3’(配列番号7)
B:5’−ATCTAACTGCTGCGCCGCCGGGAAAATACTGTACGGTTAGA−3’(配列番号8)
C:5’−CCCTAGAGTGAGTCGTATGACCCTAGAGTGAGTCGTATGAA−3’(配列番号9)。
配列
配列番号1
GTA ACG ATC CAG CTG TCA CT
配列番号2
AGT GAC AGC TGG ATC GTT AC
配列番号3
TCA TAC GAC TCA CTC TAG GG
配列番号4
CCC TAG AGT GAG TCG TAT GA
配列番号5
ACT GAC TGA CTG ACT GAC TG
配列番号6
CAG TCA GTC AGT CAG TCA GT
配列番号7
TCATACGACTCACTCTAGGGA
配列番号8
ATCTAACTGCTGCGCCGCCGGGAAAATACTGTACGGTTAGA
配列番号9
CCCTAGAGTGAGTCGTATGACCCTAGAGTGAGTCGTATGAA
Claims (17)
- アジド官能化糖を有する代謝工学の生成物ではない天然の官能基を含む表面を有する細胞であって、細胞壁を持たない細胞;及び
該天然の官能基に共有結合される核酸部分
を含む組成物。 - 細胞が初代細胞である、請求項1に記載の組成物。
- 細胞が哺乳動物細胞である、請求項1に記載の組成物。
- 細胞が幹細胞である、請求項1に記載の組成物。
- 天然の官能基が、リジン、システイン、チロシン、スレオニン、セリン、アスパラギン酸、グルタミン酸及びトリプトファンからなる群から選択されるアミノ酸を含む、請求項1に記載の組成物。
- 天然の官能基がリジンを含む、請求項1に記載の組成物。
- 核酸部分が、オリゴヌクレオチド、DNA、RNA、PNA及びアプタマーからなる群から選択されるメンバーを含む、請求項1に記載の組成物。
- 核酸部分が一本鎖DNAを含む、請求項1に記載の組成物。
- 核酸部分が約10〜約200個の核酸を含む、請求項1に記載の組成物。
- 核酸部分がアプタマーを含む、請求項1に記載の組成物。
- 核酸部分がリンカーを含む、請求項1に記載の組成物。
- 細胞表面上にリジンを含む哺乳動物細胞;及び
アミドを介してリジンに共有結合される一本鎖デオキシ核酸
を含む、請求項1に記載の組成物。 - 細胞と活性化された核酸部分とを接触させることを含む、細胞と核酸部分とのコンジュゲートを製造するための方法であって、ここで、細胞は、アジド官能化糖を有する代謝工学の生成物ではない天然の官能基を含む表面を有し、細胞は細胞壁を持たず、それにより核酸部分が天然の官能基に共有結合される方法。
- 活性化された核酸部分が活性化エステルを含む、請求項13に記載の方法。
- 哺乳動物細胞と活性化された核酸部分とを接触させることを含み、ここで、天然の官能基がリジンを含み、活性化された核酸部分がNHS−エステルを含み、それにより核酸部分がアミド結合形成によって天然の官能基に共有結合される、請求項13に記載の方法。
- 細胞表面の天然の官能基への共有結合に適した活性化された核酸部分;及び
活性化された核酸部分に相補的な核酸部分を含む基質表面であって、該天然の官能基がアジド官能化糖を有する代謝工学の生成物ではない基質表面
を含むキット。 - 細胞表面に由来し、第1の核酸部分に共有結合された天然の官能基を含む細胞表面を有する細胞;及び
細胞が第1及び第2の核酸部分の核酸二重鎖の形成を介して基質表面に結合するように、第1の核酸部分に相補的な第2の核酸部分を含む基質表面
を含むデバイスであって、ここで、細胞が細胞壁を持たず、該天然の官能基がアジド官能化糖を有する代謝工学の生成物ではないデバイス。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16774809P | 2009-04-08 | 2009-04-08 | |
US61/167,748 | 2009-04-08 | ||
US24312309P | 2009-09-16 | 2009-09-16 | |
US61/243,123 | 2009-09-16 | ||
PCT/US2010/030397 WO2010118235A1 (en) | 2009-04-08 | 2010-04-08 | Dna-cell conjugates |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016130419A Division JP2016168062A (ja) | 2009-04-08 | 2016-06-30 | Dna−細胞コンジュゲート |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2012523569A JP2012523569A (ja) | 2012-10-04 |
JP2012523569A5 JP2012523569A5 (ja) | 2013-05-30 |
JP5964746B2 true JP5964746B2 (ja) | 2016-08-03 |
Family
ID=42936579
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012504866A Active JP5964746B2 (ja) | 2009-04-08 | 2010-04-08 | Dna−細胞コンジュゲート |
JP2016130419A Pending JP2016168062A (ja) | 2009-04-08 | 2016-06-30 | Dna−細胞コンジュゲート |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016130419A Pending JP2016168062A (ja) | 2009-04-08 | 2016-06-30 | Dna−細胞コンジュゲート |
Country Status (7)
Country | Link |
---|---|
US (2) | US9327036B2 (ja) |
EP (1) | EP2417249B1 (ja) |
JP (2) | JP5964746B2 (ja) |
CN (3) | CN113186149A (ja) |
CA (1) | CA2757884C (ja) |
ES (1) | ES2924287T3 (ja) |
WO (1) | WO2010118235A1 (ja) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013019714A1 (en) | 2011-07-29 | 2013-02-07 | The Trustees Of Columbia University In The City Of New York | Mems affinity sensor for continuous monitoring of analytes |
CN104487834B (zh) | 2011-12-22 | 2018-07-17 | Bd公司 | 用于快速检测传染性微生物的方法和设备 |
US9160024B1 (en) * | 2012-06-22 | 2015-10-13 | The United States Of America, As Represented By The Secretary Of The Navy | Grafting of biomolecules onto microbial fuel cells |
WO2014160363A1 (en) * | 2013-03-14 | 2014-10-02 | Baylor Research Institute | Surface modification of porcine islets |
EP2971051A4 (en) * | 2013-03-15 | 2017-03-01 | The Trustees of Columbia University in the City of New York | Method for detecting multiple predetermined compounds in a sample |
EP2799872B1 (en) * | 2013-05-01 | 2017-10-18 | F. Hoffmann-La Roche AG | Selective release of sub-group of biological units |
CN104212758A (zh) * | 2013-05-31 | 2014-12-17 | 复旦大学 | 一种构建遗传性状嵌合多细胞结构方法 |
US11952622B2 (en) | 2013-07-18 | 2024-04-09 | The Johns Hopkins University | Analysis of DNA-containing samples and resolution of mixed contributor DNA samples |
WO2015042539A1 (en) * | 2013-09-20 | 2015-03-26 | Board Of Regents, The University Of Texas System | Fabrication of iridium oxide ph sensors and sensor arrays |
US10744207B2 (en) * | 2014-05-02 | 2020-08-18 | Acepodia, Inc. | Biological complexes and methods for using same |
WO2016022696A1 (en) | 2014-08-05 | 2016-02-11 | The Trustees Of Columbia University In The City Of New York | Method of isolating aptamers for minimal residual disease detection |
CA2993401C (en) * | 2014-10-28 | 2018-09-18 | The Governing Council Of The University Of Toronto | Electrochemical metabolic activity detecting device |
US10655097B2 (en) | 2014-12-22 | 2020-05-19 | Saint-Gobain Performance Plastics Corporation | T-cell culture double bag assembly |
US10280390B2 (en) | 2014-12-22 | 2019-05-07 | Saint-Gobain Performance Plastics Corporation | System for culture of cells in a controlled environment |
US9926524B2 (en) | 2014-12-22 | 2018-03-27 | Saint-Gobain Performance Plastics Corporation | Gas permeable material |
US11427861B2 (en) | 2016-03-17 | 2022-08-30 | Massachusetts Institute Of Technology | Methods for identifying and modulating co-occurant cellular phenotypes |
US11874268B2 (en) * | 2016-06-12 | 2024-01-16 | Nanohesgarsazan Salamat Arya Ncubation Center For Equipment And Devices | Method and system for metastasis diagnosis and prognosis |
US20200115753A1 (en) * | 2017-03-17 | 2020-04-16 | Massachusetts Institute Of Technology | Methods for identifying and modulating co-occurant cellular phenotypes |
CN107037218B (zh) * | 2017-05-04 | 2019-02-15 | 中南大学 | 一种膜蛋白检测制剂、非标记肿瘤纳米探针及使用方法 |
CN112654699A (zh) * | 2018-07-06 | 2021-04-13 | 加利福尼亚大学董事会 | 脂质修饰的寡核苷酸及其使用方法 |
US11208648B2 (en) * | 2018-11-16 | 2021-12-28 | International Business Machines Corporation | Determining position and transcriptomes of biological cells |
BR102019006678A2 (pt) * | 2019-04-02 | 2020-10-06 | Universidade Federal de Uberlândia | Processo de modificação da superfície de eletrodos para construção de biossensores eletroquímicos |
CN110205291A (zh) * | 2019-04-28 | 2019-09-06 | 蚌埠医学院第一附属医院 | 一种膜表面工程化nk细胞的制备方法及药物组合物与应用 |
CN112014361B (zh) * | 2019-05-30 | 2023-09-15 | 华东理工大学 | 一种基于多氨基荧光纳米簇的细胞膜唾液酸快速成像标记方法 |
WO2021091858A1 (en) * | 2019-11-04 | 2021-05-14 | Rarecyte, Inc. | Reference slide |
EP4055161A4 (en) | 2019-11-04 | 2024-01-17 | Bio-Rad Laboratories, Inc. | BARCODE ENCODING OF A CELL FOR SINGLE CELL SEQUENCING |
CN111534475B (zh) * | 2019-11-28 | 2022-03-15 | 厦门诺康得生物科技有限公司 | 一种细胞表面偶联抗体的方法及其应用 |
CN112280829B (zh) * | 2020-04-07 | 2023-12-26 | 南方科技大学 | 一种试剂盒、样本标记方法、单细胞测序方法 |
US20230294097A1 (en) * | 2020-05-04 | 2023-09-21 | The Regents Of The University Of California | Electrochemical cellular circuits |
WO2022099058A1 (en) * | 2020-11-09 | 2022-05-12 | The General Hospital Corporation | Methods of determining surface glycan density |
CN114574496B (zh) * | 2020-12-01 | 2024-04-09 | 上海交通大学医学院附属仁济医院 | 核苷类衍生物改性的核酸适体sgc8 |
JPWO2022190733A1 (ja) * | 2021-03-10 | 2022-09-15 | ||
CN113083383B (zh) * | 2021-03-18 | 2022-10-25 | 华中农业大学 | 微流控芯片装置、制备方法及土壤微生物群落培养方法 |
CN113092425B (zh) * | 2021-03-29 | 2022-09-27 | 上海交通大学 | 一种基于pH响应的DNA纳米机器建立可编程细胞间通讯的方法 |
US20220364160A1 (en) | 2021-05-14 | 2022-11-17 | Akoya Biosciences, Inc. | Amplification of RNA Detection Signals in Biological Samples |
US20230130371A1 (en) | 2021-08-03 | 2023-04-27 | Akoya Biosciences, Inc. | RNA Detection by Selective Labeling and Amplification |
EP4272764A1 (en) * | 2022-05-03 | 2023-11-08 | Scipio Bioscience | Method of complexing biological units with particles |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7067308B1 (en) * | 2000-03-28 | 2006-06-27 | Bioagri Corporation | Vector for genetically modifying non-human animals |
DE10019154A1 (de) | 2000-04-18 | 2001-10-31 | Univ Eberhard Karls | Zellbindende Nukleinsäuremoleküle (Aptamere) |
CN1764721A (zh) * | 2003-01-31 | 2006-04-26 | 普罗美加公司 | 官能团与蛋白质的共价束缚 |
US20060263336A1 (en) | 2003-03-24 | 2006-11-23 | Caplan Arnold I | Cell targeting methods and compositions |
US20070087400A1 (en) * | 2004-07-30 | 2007-04-19 | Aldis Darzins | Covalent tethering of functional groups to proteins and substrates therefor |
DE102006026191A1 (de) * | 2006-05-26 | 2007-11-29 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Vorrichtung und Substanz zur Isolierung von mesenchymalen Stammzellen (MSC) |
JP2007319153A (ja) * | 2006-06-02 | 2007-12-13 | Takashi Otsu | 核酸リガンドと中和剤との組み合わせ製剤 |
EP2069534A4 (en) * | 2006-08-02 | 2010-08-11 | California Inst Of Techn | METHODS AND SYSTEMS FOR DETECTING AND / OR SORTING TARGETS |
-
2010
- 2010-04-08 ES ES10762440T patent/ES2924287T3/es active Active
- 2010-04-08 JP JP2012504866A patent/JP5964746B2/ja active Active
- 2010-04-08 EP EP10762440.5A patent/EP2417249B1/en active Active
- 2010-04-08 US US13/263,129 patent/US9327036B2/en active Active
- 2010-04-08 WO PCT/US2010/030397 patent/WO2010118235A1/en active Application Filing
- 2010-04-08 CA CA2757884A patent/CA2757884C/en active Active
- 2010-04-08 CN CN202110460486.7A patent/CN113186149A/zh active Pending
- 2010-04-08 CN CN2010800213506A patent/CN102575228A/zh active Pending
- 2010-04-08 CN CN201710671296.3A patent/CN107326002A/zh active Pending
-
2016
- 2016-03-01 US US15/057,604 patent/US9969970B2/en active Active
- 2016-06-30 JP JP2016130419A patent/JP2016168062A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
CA2757884A1 (en) | 2010-10-14 |
US9969970B2 (en) | 2018-05-15 |
CN113186149A (zh) | 2021-07-30 |
EP2417249B1 (en) | 2022-06-08 |
JP2012523569A (ja) | 2012-10-04 |
US20120142088A1 (en) | 2012-06-07 |
CN107326002A (zh) | 2017-11-07 |
CN102575228A (zh) | 2012-07-11 |
EP2417249A1 (en) | 2012-02-15 |
JP2016168062A (ja) | 2016-09-23 |
US9327036B2 (en) | 2016-05-03 |
US20160319238A1 (en) | 2016-11-03 |
WO2010118235A1 (en) | 2010-10-14 |
EP2417249A4 (en) | 2013-06-26 |
ES2924287T3 (es) | 2022-10-05 |
CA2757884C (en) | 2019-10-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5964746B2 (ja) | Dna−細胞コンジュゲート | |
Kim et al. | Reversible regulation of enzyme activity by pH-responsive encapsulation in DNA nanocages | |
US20240018589A1 (en) | Method for transposase-mediated spatial tagging and analyzing genomic dna in a biological sample | |
US20230234065A1 (en) | Oligonucleotide encoded chemical libraries | |
Huang et al. | On-demand intracellular delivery of single particles in single cells by 3D hollow nanoelectrodes | |
WO2020047010A2 (en) | Increasing spatial array resolution | |
DK2494075T3 (en) | TABLE-MANAGED NANOCONJUGATES | |
US10301682B2 (en) | Fluidic device, exosome analysis method, biomolecule analysis method, and biomolecule detection method | |
Huo et al. | Nanoamplicon comparator for live-cell microRNA imaging | |
JP6453300B2 (ja) | 細胞内分析のためのナノピペット装置および方法 | |
Yin et al. | Magnetic-responsive surface-enhanced Raman scattering platform with tunable hot spot for ultrasensitive virus nucleic acid detection | |
US10538757B2 (en) | Nanozymes, methods of making nanozymes, and methods of using nanozymes | |
Chan et al. | Nanoneedle‐assisted delivery of site‐selective peptide‐functionalized DNA nanocages for targeting mitochondria and nuclei | |
WO2011068909A2 (en) | Aptamer cell compositions | |
Abune et al. | Aptamer‐functionalized hydrogels: An emerging class of biomaterials for protein delivery, cell capture, regenerative medicine, and molecular biosensing | |
US20230059921A1 (en) | Methods and compositions for diagnostically-responsive ligand-targeted delivery of therapeutic agents | |
Hsieh et al. | Graphene oxide based nanocarrier combined with a pH-sensitive tracer: a vehicle for concurrent pH sensing and pH-responsive oligonucleotide delivery | |
Mercurio et al. | Switchable protecting strategy for solid phase synthesis of DNA and RNA interacting nucleopeptides | |
CN103505739A (zh) | 一种利用滚环扩增技术制备抗肿瘤药物载体的方法 | |
Nwokwu et al. | ExoPRIME: Solid-phase immunoisolation and OMICS analysis of surface-marker-specific exosomal subpopulations | |
Roco et al. | Applications: Nanobiosystems, medicine, and health | |
Karaca et al. | Catalytic Au/PEDOT/Pt micromotors for cancer biomarker detection and potential breast cancer treatment | |
Enomoto et al. | Catch-and-release of target cells using aptamer-conjugated electroactive zwitterionic oligopeptide SAM | |
Pokhrel et al. | Mechanical Stability of DNA Corona Phase on Gold Nanospheres | |
TW201643249A (zh) | 結合於非小細胞肺癌細胞(h1975)之dna適體 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130403 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130403 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131210 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20131211 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140305 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140312 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150113 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150713 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160209 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160509 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160531 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160630 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5964746 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |