Base-sensitivity of arginine alpha-ketoamide inhibitors of serine proteases

Stoermer, Martin J., Leung, Donmienne, Young, Paul R. and Fairlie, David P. (2009) Base-sensitivity of arginine alpha-ketoamide inhibitors of serine proteases. Australian Journal of Chemistry, 62 9: 988-992. doi:10.1071/CH09150

Author Stoermer, Martin J.
Leung, Donmienne
Young, Paul R.
Fairlie, David P.
Title Base-sensitivity of arginine alpha-ketoamide inhibitors of serine proteases
Journal name Australian Journal of Chemistry   Check publisher's open access policy
ISSN 0004-9425
Publication date 2009-09-18
Year available 2009
Sub-type Article (original research)
DOI 10.1071/CH09150
Open Access Status Not Open Access
Volume 62
Issue 9
Start page 988
End page 992
Total pages 5
Editor Curt Wentrup
Place of publication Collingwood, VIC, Australia
Publisher C S I R O Publishing
Language eng
Subject C1
860899 Human Pharmaceutical Products not elsewhere classified
030599 Organic Chemistry not elsewhere classified
Abstract Serine protease enzymes use a serine hydroxyl group to catalyze hydrolysis of polypeptides. They are important in immunity, blood clotting, digestion, and as therapeutic or diagnostic targets for cancer, diabetes, stroke, inflammatory diseases, and viral infections. Their inhibitors typically possess an electrophile that reacts with the nucleophilic hydroxyl group of the catalytic serine. The α-ketoamide is a valuable electrophile in inhibitor discovery as it permits synthetic elaboration to both sides, unlike other electrophiles. Here we show that an α-ketoamide is unstable above pH 7 when adjacent to the C-terminus of arginine – the guanidine side chain condenses with the α-ketoamide at the keto group rather than the amide carbonyl to form a six-membered hemiaminal rather than a seven-membered lactam.
Keyword Chemistry, Multidisciplinary
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 19 Feb 2010, 20:35:40 EST by Susan Allen on behalf of Institute for Molecular Bioscience