CN115746081A - 一种多肽衍生物及其制备方法 - Google Patents
一种多肽衍生物及其制备方法 Download PDFInfo
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- CN115746081A CN115746081A CN202211556553.6A CN202211556553A CN115746081A CN 115746081 A CN115746081 A CN 115746081A CN 202211556553 A CN202211556553 A CN 202211556553A CN 115746081 A CN115746081 A CN 115746081A
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- 238000000034 method Methods 0.000 claims abstract description 52
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- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 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 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229960003194 meglumine Drugs 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
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
- 125000005609 naphthenate group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadecene Natural products CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 125000005480 straight-chain fatty acid group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000281 trometamol Drugs 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
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/061—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Time(min) | 0 | 30 | 52 | 57 | 57.01 | 67 |
B% | 25 | 55 | 100 | 100 | 25 | 25 |
Time(min) | 0 | 30 | 52 | 57 | 57.01 | 67 |
B% | 25 | 55 | 100 | 100 | 25 | 25 |
脱保护蛋白浓度 | 脱保护不完全样品含量(%) | 纯度(%) | 其余杂质(%) |
5mg/mL | 1.65 | 63.8 | 34.6 |
10mg/mL | 1.03 | 64.9 | 34.1 |
20mg/mL | 0.97 | 65.3 | 33.7 |
40mg/mL | 1.28 | 63.2 | 35.5 |
60mg/mL | 3.60 | 62.7 | 33.7 |
80mg/mL | 2.97 | 61.3 | 35.7 |
100mg/mL | 3.41 | 60.9 | 35.7 |
125mg/mL | 1.35 | 61.2 | 37.5 |
150mg/mL | 1.27 | 61.3 | 37.4 |
200mg/mL | 15.6 | 47.9 | 36.5 |
250mg/mL | 26.8 | 37.0 | 36.2 |
Time(min) | 0 | 30 | 52 | 57 | 57.01 | 67 |
B% | 25 | 55 | 100 | 100 | 25 | 25 |
Time(min) | 0 | 30 | 52 | 57 | 57.01 | 67 |
B% | 25 | 55 | 100 | 100 | 25 | 25 |
实验组 | 终止液条件 | 终止后pH | 终pH |
M1 | 100mL 0.2M NH<sub>4</sub>Ac+3mL 5M NaOH | N/A | 8.31 |
M2 | 100mL 0.2M Na<sub>2</sub>HPO<sub>4</sub>+2mL 5M NaOH | N/A | 7.64 |
M3 | 100mL 0.2M Tris-Base+2mL 5M NaOH | N/A | 8.05 |
M4 | 40mL 0.2M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 7.89 | 7.70 |
M5 | 30mL 0.2M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 7.93 | 7.62 |
M6 | 20mL 0.2M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 7.96 | 7.53 |
M7 | 60mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 7.87 | 7.87 |
M8 | 40mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.06 | 7.89 |
M9 | 30mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.21 | 7.87 |
M10 | 20mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.39 | 7.80 |
M11 | 10mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.61 | 7.78 |
M12 | 40mL 0.05M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.86 | 7.74 |
M13 | 30mL 0.05M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.71 | 7.65 |
M14 | 20mL 0.05M Na<sub>2</sub>HPO<sub>4</sub>+3mL 5M NaOH | 8.97 | 7.53 |
M15 | 40mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+2.0mL 5M NaOH | 6.66 | 7.51 |
M16 | 40mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+2.5mL 5M NaOH | 7.31 | 7.53 |
M17 | 40mL 0.1M Na<sub>2</sub>HPO<sub>4</sub>+3.5mL 5M NaOH | 8.74 | 7.56 |
Time(min) | 0 | 30 | 52 | 57 | 57.01 | 67 |
B% | 25 | 55 | 100 | 100 | 25 | 25 |
样品批号 | 纯度(%) | 异构体含量(%) |
批次1 | 67.3 | 4.44 |
批次2 | 65.5 | 0.76 |
批次3 | 72.0 | 2.67 |
批次4 | 69.3 | 0.85 |
批次5 | 69.9 | 1.00 |
批次6 | 73.0 | 0.74 |
批次7 | 73.6 | 7.44 |
Claims (25)
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CN202211556553.6A CN115746081B (zh) | 2022-12-06 | 2022-12-06 | 一种多肽衍生物及其制备方法 |
CN202311437284.6A CN117247422A (zh) | 2022-12-06 | 2022-12-06 | 一种多肽衍生物及其制备方法 |
CN202311437280.8A CN117229346A (zh) | 2022-12-06 | 2022-12-06 | 一种多肽衍生物及其制备方法 |
PCT/CN2023/075022 WO2024119609A1 (zh) | 2022-12-06 | 2023-02-08 | 一种多肽衍生物及其制备方法 |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US20110144012A1 (en) * | 2005-11-21 | 2011-06-16 | Dalian D.N. Bio-Engineering Co., Ltd. | Shortened glucagon-like peptide 1(sglp-1) preparation method and application |
CN109248323A (zh) * | 2017-07-14 | 2019-01-22 | 杭州先为达生物科技有限公司 | 酰化的glp-1衍生物 |
CN110386974A (zh) * | 2018-04-19 | 2019-10-29 | 杭州先为达生物科技有限公司 | Glp-1衍生物及其治疗用途 |
US20210393744A1 (en) * | 2018-04-19 | 2021-12-23 | Sciwind Biosciences Co., Ltd. | Acylated glp-1 derivative |
CN114685646A (zh) * | 2020-12-31 | 2022-07-01 | 厦门赛诺邦格生物科技股份有限公司 | 一种多肽侧链类似物的制备方法及其应用 |
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US5922810A (en) * | 1995-07-31 | 1999-07-13 | Fmc Corporation | Deprotection of protected functional polymers |
CN107033234B (zh) * | 2017-01-03 | 2018-06-26 | 北京凯因科技股份有限公司 | 酰化的glp-1衍生物 |
CN113214382B (zh) * | 2018-04-19 | 2024-01-19 | 杭州先为达生物科技股份有限公司 | 酰化的glp-1衍生物 |
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- 2022-12-06 CN CN202311437284.6A patent/CN117247422A/zh active Pending
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US20110144012A1 (en) * | 2005-11-21 | 2011-06-16 | Dalian D.N. Bio-Engineering Co., Ltd. | Shortened glucagon-like peptide 1(sglp-1) preparation method and application |
CN109248323A (zh) * | 2017-07-14 | 2019-01-22 | 杭州先为达生物科技有限公司 | 酰化的glp-1衍生物 |
CN110386974A (zh) * | 2018-04-19 | 2019-10-29 | 杭州先为达生物科技有限公司 | Glp-1衍生物及其治疗用途 |
US20210393744A1 (en) * | 2018-04-19 | 2021-12-23 | Sciwind Biosciences Co., Ltd. | Acylated glp-1 derivative |
CN114685646A (zh) * | 2020-12-31 | 2022-07-01 | 厦门赛诺邦格生物科技股份有限公司 | 一种多肽侧链类似物的制备方法及其应用 |
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CN115746081B (zh) | 2023-11-24 |
CN117229346A (zh) | 2023-12-15 |
WO2024119609A1 (zh) | 2024-06-13 |
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