| In situ neutralization in Boc-chemistry solid phase peptide synthesis. Rapid, high yield assembly of difficult sequences. | |
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MedLine Citation:
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PMID: 1478777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Simple, effective protocols have been developed for manual and machine-assisted Boc-chemistry solid phase peptide synthesis on polystyrene resins. These use in situ neutralization [i.e. neutralization simultaneous with coupling], high concentrations (> 0.2 M) of Boc-amino acid-OBt esters plus base for rapid coupling, 100% TFA for rapid Boc group removal, and a single short (30 s) DMF flow wash between deprotection/coupling and between coupling/deprotection. Single 10 min coupling times were used throughout. Overall cycle times were 15 min for manual and 19 min for machine-assisted synthesis (75 residues per day). No racemization was detected in the base-catalyzed coupling step. Several side reactions were studied, and eliminated. These included: pyrrolidonecarboxylic acid formation from Gln in hot TFA-DMF; chain-termination by reaction with excess HBTU; and, chain termination by acetylation (from HOAc in commercial Boc-amino acids). The in situ neutralization protocols gave a significant increase in the efficiency of chain assembly, especially for "difficult" sequences arising from sequence-dependent peptide chain aggregation in standard (neutralization prior to coupling) Boc-chemistry SPPS protocols or in Fmoc-chemistry SPPS. Reported syntheses include HIV-1 protease(1-50,Cys.amide), HIV-1 protease(53-99), and the full length HIV-1 protease(1-99). |
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Authors:
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M Schnölzer; P Alewood; A Jones; D Alewood; S B Kent |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of peptide and protein research Volume: 40 ISSN: 0367-8377 ISO Abbreviation: Int. J. Pept. Protein Res. Publication Date: 1992 Sep-Oct |
Date Detail:
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Created Date: 1993-02-05 Completed Date: 1993-02-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0330420 Medline TA: Int J Pept Protein Res Country: DENMARK |
Other Details:
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Languages: eng Pagination: 180-93 Citation Subset: IM; X |
Affiliation:
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Scripps Research Institute, La Jolla, CA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Acyl Carrier Protein / chemical synthesis Chromatography, High Pressure Liquid Formic Acid Esters / chemistry* Glutamine / chemistry HIV Protease / chemical synthesis Mass Spectrometry Peptide Fragments / chemical synthesis Peptides / chemical synthesis* Polystyrenes* Resins, Synthetic* Stereoisomerism Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Acyl Carrier Protein; 0/Formic Acid Esters; 0/HIV-1 protease (44-48); 0/HIV-1 protease (89-99); 0/Peptide Fragments; 0/Peptides; 0/Polystyrenes; 0/Resins, Synthetic; 0/t-butyloxycarbonyl group; 56-85-9/Glutamine; 66851-75-0/acyl carrier protein (65-74); EC 3.4.23.-/HIV Protease |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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