CN101628929B - 一种固相合成侧链保护肽链的新方法 - Google Patents
一种固相合成侧链保护肽链的新方法 Download PDFInfo
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- CN101628929B CN101628929B CN200910169385.3A CN200910169385A CN101628929B CN 101628929 B CN101628929 B CN 101628929B CN 200910169385 A CN200910169385 A CN 200910169385A CN 101628929 B CN101628929 B CN 101628929B
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 85
- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000010532 solid phase synthesis reaction Methods 0.000 title claims abstract description 10
- 239000011347 resin Substances 0.000 claims abstract description 81
- 229920005989 resin Polymers 0.000 claims abstract description 80
- 125000006239 protecting group Chemical group 0.000 claims abstract description 19
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 13
- 239000007790 solid phase Substances 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 36
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 33
- 150000001413 amino acids Chemical class 0.000 claims description 33
- 238000001914 filtration Methods 0.000 claims description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 claims description 13
- 229920001367 Merrifield resin Polymers 0.000 claims description 13
- 239000003875 Wang resin Substances 0.000 claims description 13
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 11
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 10
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 10
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 8
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- -1 benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate Chemical compound 0.000 claims description 6
- 229920003002 synthetic resin Polymers 0.000 claims description 6
- 239000000057 synthetic resin Substances 0.000 claims description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 238000001308 synthesis method Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 3
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000008961 swelling Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 239000012295 chemical reaction liquid Substances 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 150000005678 chain carbonates Chemical class 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 abstract description 10
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 238000005336 cracking Methods 0.000 abstract description 2
- 239000007791 liquid phase Substances 0.000 abstract description 2
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 12
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 description 3
- QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 1
- UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
- FZTIWOBQQYPTCJ-UHFFFAOYSA-N 4-[4-(4-carboxyphenyl)phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(O)=O)C=C1 FZTIWOBQQYPTCJ-UHFFFAOYSA-N 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- 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
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- Peptides Or Proteins (AREA)
Abstract
Description
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN200910169385.3A CN101628929B (zh) | 2009-08-27 | 2009-08-27 | 一种固相合成侧链保护肽链的新方法 |
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CN200910169385.3A CN101628929B (zh) | 2009-08-27 | 2009-08-27 | 一种固相合成侧链保护肽链的新方法 |
Publications (2)
Publication Number | Publication Date |
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CN101628929A CN101628929A (zh) | 2010-01-20 |
CN101628929B true CN101628929B (zh) | 2014-09-17 |
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CN200910169385.3A Expired - Fee Related CN101628929B (zh) | 2009-08-27 | 2009-08-27 | 一种固相合成侧链保护肽链的新方法 |
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Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102304167B (zh) * | 2011-07-20 | 2013-06-05 | 北京中科亚光生物科技有限公司 | 一种合成含有天冬氨酸-精氨酸及衍生物单元的多肽的新方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003093301A2 (en) * | 2002-05-03 | 2003-11-13 | Avecia Limited | Process for the synthesis of peptides |
WO2005100378A1 (en) * | 2004-04-13 | 2005-10-27 | Avecia Limited | Process for the preparation of a peptide, and compounds comprising a thioester carboxyl-activating group for use therein |
WO2008062391A2 (en) * | 2006-11-21 | 2008-05-29 | Ipsen Manufacturing Ireland Limited | Boc and fmoc solid phase peptide synthesis |
CN101437838A (zh) * | 2006-05-03 | 2009-05-20 | 马林克罗特公司 | 用于从树脂上释放保护的肽的组合物和方法 |
-
2009
- 2009-08-27 CN CN200910169385.3A patent/CN101628929B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003093301A2 (en) * | 2002-05-03 | 2003-11-13 | Avecia Limited | Process for the synthesis of peptides |
WO2005100378A1 (en) * | 2004-04-13 | 2005-10-27 | Avecia Limited | Process for the preparation of a peptide, and compounds comprising a thioester carboxyl-activating group for use therein |
CN101437838A (zh) * | 2006-05-03 | 2009-05-20 | 马林克罗特公司 | 用于从树脂上释放保护的肽的组合物和方法 |
WO2008062391A2 (en) * | 2006-11-21 | 2008-05-29 | Ipsen Manufacturing Ireland Limited | Boc and fmoc solid phase peptide synthesis |
Non-Patent Citations (2)
Title |
---|
欧阳嘉 等."Fmoc(9-茐甲基氧羰基)法固相合成胸腺五肽".《南京工业大学学报》.2005,第27卷(第3期),第61-64页. |
欧阳嘉 等."Fmoc(9-茐甲基氧羰基)法固相合成胸腺五肽".《南京工业大学学报》.2005,第27卷(第3期),第61-64页. * |
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CB02 | Change of applicant information |
Address after: 102205 Beijing city center Changping District Yangfang Town North Hospital No. Applicant after: The Chemical Defense College of PLA Address before: 102205 Beijing city center Changping District Yangfang Town North Hospital No. Applicant before: Antichemical Command Engineering College P. L. A. |
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COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: ANTICHEMICAL COMMAND ENGINEERING COLLEGE P.L.A. TO: PLA INSTITUTE OF CHEMICAL DEFENSE |
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Granted publication date: 20140917 Termination date: 20150827 |
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