CA2590837A1 - Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta. - Google Patents

Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta. Download PDF

Info

Publication number: CA2590837A1
Authority: CA; Canada
Prior art keywords: seq; beta; tgf; peptide; tsp
Prior art date: 1993-08-13
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.): Abandoned

Application number

CA002590837A

Other languages

English (en)

Inventor

Joanne E. Murphy-Ullrich

David D. Roberts

Henry C. Krutzsch

Stacey Schultz-Cherry

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

US Department of Health and Human Services

UAB Research Foundation

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1993-08-13

Filing date

1994-08-12

Publication date

1995-02-23

1994-08-12 Application filed by Individual filed Critical Individual

1994-08-12 Priority claimed from CA002169360A external-priority patent/CA2169360A1/fr

1995-02-23 Publication of CA2590837A1 publication Critical patent/CA2590837A1/fr

Status Abandoned legal-status Critical Current

Links

230000000694 effects Effects 0.000 title claims abstract description 116
238000000034 method Methods 0.000 title claims abstract description 75
230000002401 inhibitory effect Effects 0.000 title claims abstract description 65
230000004936 stimulating effect Effects 0.000 title claims abstract description 15
239000000203 mixture Substances 0.000 title description 4
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 254
150000001413 amino acids Chemical class 0.000 claims abstract description 131
230000004913 activation Effects 0.000 claims abstract description 81
206010052428 Wound Diseases 0.000 claims abstract description 56
208000027418 Wounds and injury Diseases 0.000 claims abstract description 56
206010016654 Fibrosis Diseases 0.000 claims abstract description 55
230000004761 fibrosis Effects 0.000 claims abstract description 55
230000029663 wound healing Effects 0.000 claims abstract description 51
230000003213 activating effect Effects 0.000 claims abstract description 49
210000002889 endothelial cell Anatomy 0.000 claims abstract description 31
230000001404 mediated effect Effects 0.000 claims abstract description 26
230000000638 stimulation Effects 0.000 claims abstract description 25
239000003446 ligand Substances 0.000 claims abstract description 20
238000006243 chemical reaction Methods 0.000 claims abstract description 19
230000035755 proliferation Effects 0.000 claims abstract description 19
230000002829 reductive effect Effects 0.000 claims abstract description 10
230000000903 blocking effect Effects 0.000 claims abstract description 8
230000002708 enhancing effect Effects 0.000 claims abstract description 8
230000007170 pathology Effects 0.000 claims abstract description 8
230000010046 negative regulation of endothelial cell proliferation Effects 0.000 claims abstract description 7
102000002938 Thrombospondin Human genes 0.000 claims description 161
108060008245 Thrombospondin Proteins 0.000 claims description 161
ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)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)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)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](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 43
102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 42
108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 42
108010088429 glycyl-glycyl-tryptophyl-seryl-histidyl-tryptophan Proteins 0.000 claims description 31
108091000042 riboflavin kinase Proteins 0.000 claims description 22
YOKXDNNIFSAXBY-QAETUUGQSA-N (2s)-6-amino-n-[(2s)-1-amino-4-methyl-1-oxopentan-2-yl]-2-[[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanamide Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O YOKXDNNIFSAXBY-QAETUUGQSA-N 0.000 claims description 9
230000036961 partial effect Effects 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 4
229920003169 water-soluble polymer Polymers 0.000 claims description 3
235000001014 amino acid Nutrition 0.000 description 117
210000004027 cell Anatomy 0.000 description 92
102000004196 processed proteins & peptides Human genes 0.000 description 71
230000000692 anti-sense effect Effects 0.000 description 46
229920001817 Agar Polymers 0.000 description 26
239000008272 agar Substances 0.000 description 26
WJKXMMKXXDAANJ-DZUOILHNSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)CN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CN=CN1 WJKXMMKXXDAANJ-DZUOILHNSA-N 0.000 description 25
239000012091 fetal bovine serum Substances 0.000 description 24
239000003636 conditioned culture medium Substances 0.000 description 22
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 20
108090000623 proteins and genes Proteins 0.000 description 20
102000004169 proteins and genes Human genes 0.000 description 19
235000018102 proteins Nutrition 0.000 description 18
238000003556 assay Methods 0.000 description 17
210000001772 blood platelet Anatomy 0.000 description 16
230000015572 biosynthetic process Effects 0.000 description 15
230000005757 colony formation Effects 0.000 description 15
230000012010 growth Effects 0.000 description 15
238000001727 in vivo Methods 0.000 description 14
239000000126 substance Substances 0.000 description 13
230000027455 binding Effects 0.000 description 12
210000001519 tissue Anatomy 0.000 description 12
241000700159 Rattus Species 0.000 description 11
102000009618 Transforming Growth Factors Human genes 0.000 description 11
108010009583 Transforming Growth Factors Proteins 0.000 description 11
230000005764 inhibitory process Effects 0.000 description 11
239000002609 medium Substances 0.000 description 11
238000012216 screening Methods 0.000 description 11
108010035532 Collagen Proteins 0.000 description 10
102000008186 Collagen Human genes 0.000 description 10
108010088842 Fibrinolysin Proteins 0.000 description 10
229920001436 collagen Polymers 0.000 description 10
230000006870 function Effects 0.000 description 10
239000007924 injection Substances 0.000 description 10
238000002347 injection Methods 0.000 description 10
108010053062 lysyl-arginyl-phenylalanyl-lysine Proteins 0.000 description 10
229940012957 plasmin Drugs 0.000 description 10
125000003275 alpha amino acid group Chemical group 0.000 description 9
230000001419 dependent effect Effects 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
230000001965 increasing effect Effects 0.000 description 9
238000006467 substitution reaction Methods 0.000 description 9
108091003079 Bovine Serum Albumin Proteins 0.000 description 8
102400000401 Latency-associated peptide Human genes 0.000 description 8
101800001155 Latency-associated peptide Proteins 0.000 description 8
GGNOBVSOZPHLCE-GUBZILKMSA-N Lys-Gln-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O GGNOBVSOZPHLCE-GUBZILKMSA-N 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
108010047857 aspartylglycine Proteins 0.000 description 8
238000004166 bioassay Methods 0.000 description 8
230000001131 transforming effect Effects 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 7
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 7
230000004663 cell proliferation Effects 0.000 description 7
230000001332 colony forming effect Effects 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
150000008574 D-amino acids Chemical class 0.000 description 6
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
230000033115 angiogenesis Effects 0.000 description 6
229940098773 bovine serum albumin Drugs 0.000 description 6
230000021164 cell adhesion Effects 0.000 description 6
230000001413 cellular effect Effects 0.000 description 6
238000010293 colony formation assay Methods 0.000 description 6
210000002744 extracellular matrix Anatomy 0.000 description 6
229920000669 heparin Polymers 0.000 description 6
229960002897 heparin Drugs 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
230000003993 interaction Effects 0.000 description 6
230000007246 mechanism Effects 0.000 description 6
239000002243 precursor Substances 0.000 description 6
238000012545 processing Methods 0.000 description 6
108010088751 Albumins Proteins 0.000 description 5
102000009027 Albumins Human genes 0.000 description 5
102100037362 Fibronectin Human genes 0.000 description 5
108010067306 Fibronectins Proteins 0.000 description 5
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 5
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
244000309466 calf Species 0.000 description 5
230000010261 cell growth Effects 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
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 5
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 5
230000003511 endothelial effect Effects 0.000 description 5
210000002950 fibroblast Anatomy 0.000 description 5
229960002591 hydroxyproline Drugs 0.000 description 5
238000005259 measurement Methods 0.000 description 5
239000002953 phosphate buffered saline Substances 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
230000004044 response Effects 0.000 description 5
210000000329 smooth muscle myocyte Anatomy 0.000 description 5
238000012360 testing method Methods 0.000 description 5
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 5
SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 4
206010003445 Ascites Diseases 0.000 description 4
UPADCCSMVOQAGF-LBPRGKRZSA-N Gly-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)CN)C(O)=O)=CNC2=C1 UPADCCSMVOQAGF-LBPRGKRZSA-N 0.000 description 4
101000848647 Homo sapiens Telomerase RNA component interacting RNase Proteins 0.000 description 4
FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 4
BVLGVLWFIZFEAH-BPUTZDHNSA-N Ser-Pro-Trp Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O BVLGVLWFIZFEAH-BPUTZDHNSA-N 0.000 description 4
102100034592 Telomerase RNA component interacting RNase Human genes 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000003501 co-culture Methods 0.000 description 4
230000000875 corresponding effect Effects 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
230000004069 differentiation Effects 0.000 description 4
239000012634 fragment Substances 0.000 description 4
239000008103 glucose Substances 0.000 description 4
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
239000003102 growth factor Substances 0.000 description 4
230000009036 growth inhibition Effects 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
-1 polypropylene Polymers 0.000 description 4
230000008569 process Effects 0.000 description 4
238000011552 rat model Methods 0.000 description 4
230000001105 regulatory effect Effects 0.000 description 4
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 4
QUBKBPZGMZWOKQ-SZMVWBNQSA-N Arg-Trp-Arg Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 QUBKBPZGMZWOKQ-SZMVWBNQSA-N 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
108010042955 Calcineurin Proteins 0.000 description 3
102000004631 Calcineurin Human genes 0.000 description 3
108091035707 Consensus sequence Proteins 0.000 description 3
102400001368 Epidermal growth factor Human genes 0.000 description 3
101800003838 Epidermal growth factor Proteins 0.000 description 3
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
229920001917 Ficoll Polymers 0.000 description 3
102000019218 Mannose-6-phosphate receptors Human genes 0.000 description 3
NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 3
108010022999 Serine Proteases Proteins 0.000 description 3
102000012479 Serine Proteases Human genes 0.000 description 3
108090000190 Thrombin Proteins 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
230000033228 biological regulation Effects 0.000 description 3
150000001720 carbohydrates Chemical group 0.000 description 3
230000009087 cell motility Effects 0.000 description 3
238000001516 cell proliferation assay Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000011161 development Methods 0.000 description 3
230000018109 developmental process Effects 0.000 description 3
230000002900 effect on cell Effects 0.000 description 3
229940116977 epidermal growth factor Drugs 0.000 description 3
230000002055 immunohistochemical effect Effects 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
230000003472 neutralizing effect Effects 0.000 description 3
239000002674 ointment Substances 0.000 description 3
238000003752 polymerase chain reaction Methods 0.000 description 3
230000002265 prevention Effects 0.000 description 3
230000002797 proteolythic effect Effects 0.000 description 3
239000000523 sample Substances 0.000 description 3
230000028327 secretion Effects 0.000 description 3
239000000243 solution Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
229960004072 thrombin Drugs 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
QUBKBPZGMZWOKQ-UHFFFAOYSA-N 2-[[2-[[2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C1=CC=C2C(CC(NC(=O)C(CCCN=C(N)N)N)C(=O)NC(CCCN=C(N)N)C(O)=O)=CNC2=C1 QUBKBPZGMZWOKQ-UHFFFAOYSA-N 0.000 description 2
INXWADWANGLMPJ-UHFFFAOYSA-N 2-[[2-[[2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(N)=NCCCC(N)C(=O)NC(C(=O)NC(CCCN=C(N)N)C(O)=O)CC1=CC=CC=C1 INXWADWANGLMPJ-UHFFFAOYSA-N 0.000 description 2
108010039627 Aprotinin Proteins 0.000 description 2
KZXPVYVSHUJCEO-ULQDDVLXSA-N Arg-Phe-Lys Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CC=CC=C1 KZXPVYVSHUJCEO-ULQDDVLXSA-N 0.000 description 2
NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical group OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 2
108020004414 DNA Proteins 0.000 description 2
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
241000287828 Gallus gallus Species 0.000 description 2
CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
108010031792 IGF Type 2 Receptor Proteins 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
108050006616 Mannose-6-phosphate receptors Proteins 0.000 description 2
101000666901 Oxyuranus scutellatus scutellatus Kunitz-type serine protease inhibitor taicotoxin Proteins 0.000 description 2
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 2
239000004743 Polypropylene Substances 0.000 description 2
FYUIFUJFNCLUIX-XVYDVKMFSA-N Ser-His-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O FYUIFUJFNCLUIX-XVYDVKMFSA-N 0.000 description 2
NBUKGEFVZJMSIS-XIRDDKMYSA-N Ser-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)[C@H](CO)N NBUKGEFVZJMSIS-XIRDDKMYSA-N 0.000 description 2
VFWQQZMRKFOGLE-ZLUOBGJFSA-N Ser-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O VFWQQZMRKFOGLE-ZLUOBGJFSA-N 0.000 description 2
VDCGPCSLAJAKBB-XIRDDKMYSA-N Trp-Ser-His Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N VDCGPCSLAJAKBB-XIRDDKMYSA-N 0.000 description 2
GEGYPBOPIGNZIF-CWRNSKLLSA-N Trp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)O GEGYPBOPIGNZIF-CWRNSKLLSA-N 0.000 description 2
ARKBYVBCEOWRNR-UBHSHLNASA-N Trp-Ser-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O ARKBYVBCEOWRNR-UBHSHLNASA-N 0.000 description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000009471 action Effects 0.000 description 2
102000003801 alpha-2-Antiplasmin Human genes 0.000 description 2
108090000183 alpha-2-Antiplasmin Proteins 0.000 description 2
150000001412 amines Chemical group 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
229960004405 aprotinin Drugs 0.000 description 2
108010094001 arginyl-tryptophyl-arginine Proteins 0.000 description 2
230000003305 autocrine Effects 0.000 description 2
210000001043 capillary endothelial cell Anatomy 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
230000003915 cell function Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
210000002808 connective tissue Anatomy 0.000 description 2
238000012217 deletion Methods 0.000 description 2
230000037430 deletion Effects 0.000 description 2
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
210000002919 epithelial cell Anatomy 0.000 description 2
230000008556 epithelial cell proliferation Effects 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
210000001650 focal adhesion Anatomy 0.000 description 2
230000004927 fusion Effects 0.000 description 2
208000005017 glioblastoma Diseases 0.000 description 2
XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
201000001441 melanoma Diseases 0.000 description 2
239000003226 mitogen Substances 0.000 description 2
210000003098 myoblast Anatomy 0.000 description 2
239000013642 negative control Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
238000010647 peptide synthesis reaction Methods 0.000 description 2
210000003668 pericyte Anatomy 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
210000001316 polygonal cell Anatomy 0.000 description 2
229920001184 polypeptide Polymers 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
239000013641 positive control Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
239000003001 serine protease inhibitor Substances 0.000 description 2
108010026333 seryl-proline Proteins 0.000 description 2
238000002741 site-directed mutagenesis Methods 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
230000017423 tissue regeneration Effects 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
239000013638 trimer Substances 0.000 description 2
101150060219 tsp-1 gene Proteins 0.000 description 2
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
KQFRUSHJPKXBMB-BHDSKKPTSA-N Ala-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 KQFRUSHJPKXBMB-BHDSKKPTSA-N 0.000 description 1
CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 1
HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 1
TVUFMYKTYXTRPY-HERUPUMHSA-N Ala-Trp-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O TVUFMYKTYXTRPY-HERUPUMHSA-N 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
BJNUAWGXPSHQMJ-DCAQKATOSA-N Arg-Gln-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O BJNUAWGXPSHQMJ-DCAQKATOSA-N 0.000 description 1
KRQSPVKUISQQFS-FJXKBIBVSA-N Arg-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N KRQSPVKUISQQFS-FJXKBIBVSA-N 0.000 description 1
MJINRRBEMOLJAK-DCAQKATOSA-N Arg-Lys-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N MJINRRBEMOLJAK-DCAQKATOSA-N 0.000 description 1
NGTYEHIRESTSRX-UWVGGRQHSA-N Arg-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NGTYEHIRESTSRX-UWVGGRQHSA-N 0.000 description 1
GRRXPUAICOGISM-RWMBFGLXSA-N Arg-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GRRXPUAICOGISM-RWMBFGLXSA-N 0.000 description 1
INXWADWANGLMPJ-JYJNAYRXSA-N Arg-Phe-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CC1=CC=CC=C1 INXWADWANGLMPJ-JYJNAYRXSA-N 0.000 description 1
FVBZXNSRIDVYJS-AVGNSLFASA-N Arg-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N FVBZXNSRIDVYJS-AVGNSLFASA-N 0.000 description 1
208000002109 Argyria Diseases 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
NRIFEOUAFLTMFJ-AAEUAGOBSA-N Asp-Gly-Trp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O NRIFEOUAFLTMFJ-AAEUAGOBSA-N 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
206010055665 Corneal neovascularisation Diseases 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
108700024394 Exon Proteins 0.000 description 1
108010054218 Factor VIII Proteins 0.000 description 1
102000001690 Factor VIII Human genes 0.000 description 1
102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
ZFADFBPRMSBPOT-KKUMJFAQSA-N Gln-Arg-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O ZFADFBPRMSBPOT-KKUMJFAQSA-N 0.000 description 1
NJCALAAIGREHDR-WDCWCFNPSA-N Glu-Leu-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NJCALAAIGREHDR-WDCWCFNPSA-N 0.000 description 1
102000005720 Glutathione transferase Human genes 0.000 description 1
108010070675 Glutathione transferase Proteins 0.000 description 1
PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
WDXLKVQATNEAJQ-BQBZGAKWSA-N Gly-Pro-Asp Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WDXLKVQATNEAJQ-BQBZGAKWSA-N 0.000 description 1
ISSDODCYBOWWIP-GJZGRUSLSA-N Gly-Pro-Trp Chemical compound [H]NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O ISSDODCYBOWWIP-GJZGRUSLSA-N 0.000 description 1
ONSARSFSJHTMFJ-STQMWFEESA-N Gly-Trp-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O ONSARSFSJHTMFJ-STQMWFEESA-N 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
229920002683 Glycosaminoglycan Polymers 0.000 description 1
108010043490 Hep I peptide Proteins 0.000 description 1
230000010556 Heparin Binding Activity Effects 0.000 description 1
CJGDTAHEMXLRMB-ULQDDVLXSA-N His-Arg-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O CJGDTAHEMXLRMB-ULQDDVLXSA-N 0.000 description 1
101000829419 Homo sapiens Spermatogenic leucine zipper protein 1 Proteins 0.000 description 1
101000659879 Homo sapiens Thrombospondin-1 Proteins 0.000 description 1
101000633605 Homo sapiens Thrombospondin-2 Proteins 0.000 description 1
206010062016 Immunosuppression Diseases 0.000 description 1
102100025947 Insulin-like growth factor II Human genes 0.000 description 1
SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
108010085895 Laminin Proteins 0.000 description 1
ADJWHHZETYAAAX-SRVKXCTJSA-N Leu-Ser-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ADJWHHZETYAAAX-SRVKXCTJSA-N 0.000 description 1
AMSSKPUHBUQBOQ-SRVKXCTJSA-N Leu-Ser-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N AMSSKPUHBUQBOQ-SRVKXCTJSA-N 0.000 description 1
YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 1
WXJKFRMKJORORD-DCAQKATOSA-N Lys-Arg-Ala Chemical compound NC(=N)NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CCCCN WXJKFRMKJORORD-DCAQKATOSA-N 0.000 description 1
WALVCOOOKULCQM-ULQDDVLXSA-N Lys-Arg-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WALVCOOOKULCQM-ULQDDVLXSA-N 0.000 description 1
NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 1
NLOZZWJNIKKYSC-WDSOQIARSA-N Lys-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CCCCN)C(O)=O)=CNC2=C1 NLOZZWJNIKKYSC-WDSOQIARSA-N 0.000 description 1
GGAPIOORBXHMNY-ULQDDVLXSA-N Lys-Arg-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N)O GGAPIOORBXHMNY-ULQDDVLXSA-N 0.000 description 1
PGBPWPTUOSCNLE-JYJNAYRXSA-N Lys-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N PGBPWPTUOSCNLE-JYJNAYRXSA-N 0.000 description 1
ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 1
PLDJDCJLRCYPJB-VOAKCMCISA-N Lys-Lys-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PLDJDCJLRCYPJB-VOAKCMCISA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
108010090665 Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Proteins 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
241001529936 Murinae Species 0.000 description 1
230000004988 N-glycosylation Effects 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
239000004105 Penicillin G potassium Substances 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
102000004211 Platelet factor 4 Human genes 0.000 description 1
108090000778 Platelet factor 4 Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
VBZXFFYOBDLLFE-HSHDSVGOSA-N Pro-Trp-Thr Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H]([C@H](O)C)C(O)=O)C(=O)[C@@H]1CCCN1 VBZXFFYOBDLLFE-HSHDSVGOSA-N 0.000 description 1
102100038567 Properdin Human genes 0.000 description 1
108010005642 Properdin Proteins 0.000 description 1
239000004365 Protease Substances 0.000 description 1
108010003201 RGH 0205 Proteins 0.000 description 1
108091006629 SLC13A2 Proteins 0.000 description 1
206010070834 Sensitisation Diseases 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 1
WEQAYODCJHZSJZ-KKUMJFAQSA-N Ser-His-Tyr Chemical compound C([C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CN=CN1 WEQAYODCJHZSJZ-KKUMJFAQSA-N 0.000 description 1
LPSKHZWBQONOQJ-XIRDDKMYSA-N Ser-Lys-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N LPSKHZWBQONOQJ-XIRDDKMYSA-N 0.000 description 1
ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
102000007000 Tenascin Human genes 0.000 description 1
108010008125 Tenascin Proteins 0.000 description 1
DGDCHPCRMWEOJR-FQPOAREZSA-N Thr-Ala-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DGDCHPCRMWEOJR-FQPOAREZSA-N 0.000 description 1
MQBTXMPQNCGSSZ-OSUNSFLBSA-N Thr-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CCCN=C(N)N MQBTXMPQNCGSSZ-OSUNSFLBSA-N 0.000 description 1
IMULJHHGAUZZFE-MBLNEYKQSA-N Thr-Gly-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IMULJHHGAUZZFE-MBLNEYKQSA-N 0.000 description 1
102100036034 Thrombospondin-1 Human genes 0.000 description 1
102100029529 Thrombospondin-2 Human genes 0.000 description 1
102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
BRBCKMMXKONBAA-KWBADKCTSA-N Trp-Ala-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 BRBCKMMXKONBAA-KWBADKCTSA-N 0.000 description 1
DXDMNBJJEXYMLA-UBHSHLNASA-N Trp-Asn-Asp Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O)=CNC2=C1 DXDMNBJJEXYMLA-UBHSHLNASA-N 0.000 description 1
UPOGHWJJZAZNSW-XIRDDKMYSA-N Trp-His-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O UPOGHWJJZAZNSW-XIRDDKMYSA-N 0.000 description 1
MYVYPSWUSKCCHG-JQWIXIFHSA-N Trp-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 MYVYPSWUSKCCHG-JQWIXIFHSA-N 0.000 description 1
BZDGLJPROOOUOZ-XGEHTFHBSA-N Val-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N)O BZDGLJPROOOUOZ-XGEHTFHBSA-N 0.000 description 1
108010031318 Vitronectin Proteins 0.000 description 1
102100035140 Vitronectin Human genes 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
230000001133 acceleration Effects 0.000 description 1
108010022164 acetyl-LDL Proteins 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
238000002814 agar dilution Methods 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
230000019552 anatomical structure morphogenesis Effects 0.000 description 1
229920001586 anionic polysaccharide Polymers 0.000 description 1
150000004836 anionic polysaccharides Chemical class 0.000 description 1
230000000181 anti-adherent effect Effects 0.000 description 1
230000000702 anti-platelet effect Effects 0.000 description 1
239000003146 anticoagulant agent Substances 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
210000000709 aorta Anatomy 0.000 description 1
210000004618 arterial endothelial cell Anatomy 0.000 description 1
208000011775 arteriosclerosis disease Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
210000002469 basement membrane Anatomy 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000001851 biosynthetic effect Effects 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000034196 cell chemotaxis Effects 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
230000015861 cell surface binding Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
230000003196 chaotropic effect Effects 0.000 description 1
244000221110 common millet Species 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000011109 contamination Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
201000000159 corneal neovascularization Diseases 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
108010018866 cysteinyl-seryl-valyl-threonyl-cysteinyl-glycine Proteins 0.000 description 1
108010016616 cysteinylglycine Proteins 0.000 description 1
102000003675 cytokine receptors Human genes 0.000 description 1
108010057085 cytokine receptors Proteins 0.000 description 1
230000034994 death Effects 0.000 description 1
230000007423 decrease Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000022811 deglycosylation Effects 0.000 description 1
230000003413 degradative effect Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
230000003467 diminishing effect Effects 0.000 description 1
230000006334 disulfide bridging Effects 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000003182 dose-response assay Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
239000012636 effector Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
229960000301 factor viii Drugs 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000020764 fibrinolysis Effects 0.000 description 1
229940126864 fibroblast growth factor Drugs 0.000 description 1
230000003328 fibroblastic effect Effects 0.000 description 1
230000009795 fibrotic process Effects 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
108010078326 glycyl-glycyl-valine Proteins 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000037313 granulation tissue formation Effects 0.000 description 1
230000009422 growth inhibiting effect Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
230000035876 healing Effects 0.000 description 1
108010018006 histidylserine Proteins 0.000 description 1
239000000710 homodimer Substances 0.000 description 1
102000049483 human SPZ1 Human genes 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
208000011379 keloid formation Diseases 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
108010053037 kyotorphin Proteins 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000012092 media component Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
108091005601 modified peptides Proteins 0.000 description 1
230000035407 negative regulation of cell proliferation Effects 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
230000003076 paracrine Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
235000019368 penicillin G potassium Nutrition 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
108010091748 peptide A Proteins 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
230000030393 positive regulation of fibroblast proliferation Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
238000007388 punch biopsy Methods 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
239000012488 sample solution Substances 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000008313 sensitization Effects 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
108010048818 seryl-histidine Proteins 0.000 description 1
108010048397 seryl-lysyl-leucine Proteins 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
241000894007 species Species 0.000 description 1
210000004989 spleen cell Anatomy 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
238000010186 staining Methods 0.000 description 1
229960002385 streptomycin sulfate Drugs 0.000 description 1
239000013589 supplement Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
108010061238 threonyl-glycine Proteins 0.000 description 1
229940099456 transforming growth factor beta 1 Drugs 0.000 description 1
108010045269 tryptophyltryptophan Proteins 0.000 description 1
108010051110 tyrosyl-lysine Proteins 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000001262 western blot Methods 0.000 description 1

Landscapes

Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002590837A 1993-08-13 1994-08-12 Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta. Abandoned CA2590837A1 (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US10612093A	1993-08-13	1993-08-13
US08/106,120		1993-08-13
US23816994A	1994-05-04	1994-05-04
US08/238,169		1994-05-04
CA002169360A CA2169360A1 (fr)	1993-08-13	1994-08-12	Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta.

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002169360A Division CA2169360A1 (fr)	1993-08-13	1994-08-12	Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta.

Publications (1)

Publication Number	Publication Date
CA2590837A1 true CA2590837A1 (fr)	1995-02-23

Family

ID=38445928

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002590837A Abandoned CA2590837A1 (fr)	1993-08-13	1994-08-12	Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta.

Country Status (1)

Country	Link
CA (1)	CA2590837A1 (fr)

1994
- 1994-08-12 CA CA002590837A patent/CA2590837A1/fr not_active Abandoned

Legal Events

Date	Code	Title	Description
2007-06-18	EEER	Examination request
2010-08-12	FZDE	Dead

Publication	Publication Date	Title
EP0716609B1 (fr)	2005-12-28	Procedes et compositions utiles pour stimuler et inhiber l'activite du facteur de croissance transformant de type beta
Schultz-Cherry et al.	1993	Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism
US5849701A (en)	1998-12-15	Peptide inhibitors of fibronectin and related collagen-binding proteins
Brown et al.	1997	The C‐terminal domain V of perlecan promotes β1 integrin‐mediated cell adhesion, binds heparin, nidogen and fibulin‐2 and can be modified by glycosaminoglycans
Mooradian et al.	1993	Characterization of FN-C/HV, a novel synthetic peptide from fibronectin that promotes rabbit corneal epithelial cell adhesion, spreading, and motility.
US5703045A (en)	1997-12-30	Treating disorders by application of insulin-like growth factors and analogs
ES2680022T3 (es)	2018-09-03	Fragmentos peptídicos para inducir la síntesis de proteínas de la matriz extracelular
CA2058443C (fr)	1998-11-03	Traitement de certains troubles par application de facteurs de croissance insulinoides et de leurs analogues
EP0494264B1 (fr)	1997-06-18	Inhibition de facteur de croissance a transformation afin d'empecher l'accumulation de matrice extracellulaire
US8691944B2 (en)	2014-04-08	Fibronectin polypeptides and methods of use
WO1994011395A9 (fr)	1995-03-02	Inhibiteurs peptidiques de la fibronectine et proteines de liaison au collagene apparentees
HUT61322A (en)	1992-12-28	Process for producing peptide derivatives suitable for treating glaucoma and pharmaceutical compositions comprising same as active ingredient
Vartio et al.	1983	Fibronectin: chains of domains with diversified functions
AU761451B2 (en)	2003-06-05	NCAM binding compounds
US6469138B1 (en)	2002-10-22	Thrombospondin receptor binding peptides
US6906170B1 (en)	2005-06-14	Anti-inflammatory peptides derived from IL-2 and analogues thereof
EP0514721A1 (fr)	1992-11-25	Peptides ayant une activité de type thrombospondine et leur utilisation thérapeutique
US5453489A (en)	1995-09-26	Polypeptide fragments of fibronectin which can modulate extracellular matrix assembly
Sephel et al.	1989	A laminin-pepsin fragment with cell attachment and neurite outgrowth activity at distinct sites
CA2590837A1 (fr)	1995-02-23	Methodes et compositions pour la stimulation et l'inhibition de l'activite de tgf-.beta.
Huber et al.	1991	Activation of human platelet-derived latent transforming growth factor-β 1 by human glioblastoma cells. Comparison with proteolytic and glycosidic enzymes
Mooradian et al.	1992	Rabbit corneal epithelial cells adhere to two distinct heparin-binding synthetic peptides derived from fibronectin.
JP3951676B2 (ja)	2007-08-01	オリゴペプチド
JP4168623B2 (ja)	2008-10-22	オリゴペプチド
SCHULTZ-CHERRY et al.	0	THROMBOSPODNIN BINDS AND ACTIVATES THE SMALL AND LARGE FORMS OF LATENT TRANSFORMING GROWTH FACTOR-B IN A CHEMICALLY-DEFINED SYSTEM