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PMID: 2395797 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Chemical pathways of peptide degradation. II. Kinetics of deamidation of an asparaginyl residue in a model hexapeptide.

Pharmaceutical research ·Vol. 7 ·No. 7 ·1990-07-00 ·Pages 703-11

Patel K, Borchardt RT

Abstract

Deamidation of Asn residues is a major chemical pathway of degradation of peptides and proteins. To understand better the external factors that influence deamidation, we studied the degradation of the hexapeptide Val-Tyr-Pro-Asn-Gly-Ala, a fragment of adrenocorticotropic hormone, by HPLC. The deamidation of this model peptide showed marked dependence on pH, temperature, and buffer composition. In the pH range 5 to 12, the peptide deamidated exclusively via a cyclic imide intermediate with the formation of both the Asp- and the isoAsp-hexapeptides. Buffer catalysis was also observed in the pH range of 7 to 11. However, at acidic pH's, the pathway of deamidation involved direct hydrolysis of the amide side chain of Asn residue to produce only the Asp-hexapeptide.

MeSH Terms
Amides/analysis Amino Acid Sequence Asparagine/analysis Buffers Chromatography, High Pressure Liquid Hydrogen-Ion Concentration Hydrolysis Kinetics Models, Chemical Molecular Sequence Data Oligopeptides/analysis,pharmacokinetics Peptide Fragments/analysis,pharmacokinetics Temperature
Chemicals
Amides Buffers Oligopeptides Peptide Fragments valyl-tyrosyl-prolyl-asparaginyl-glycyl-alanine Asparagine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Patel K
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Borchardt R T
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32 references, click to expand
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Article Info
Journal
Pharmaceutical research
Abbr.
Pharm Res
ISSN
0724-8741
DOI
10.1023/a:1015807303766
Published
1990-07-00
Pages
703-11
Language
English
Region
United States
NLM ID
8406521
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1015807303766 View journal details
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