期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 62, 期 -, 页码 199-205出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.12.043
关键词
Agmatine; Peptide; West Nile virus; NS2B/NS3; Serine protease inhibitor
资金
- A*STAR Biomedical Research Council
This communication describes the synthesis and inhibitory activities of thirty-seven novel C-terminal agmatine dipeptides used as screening compounds to study the structure-activity relationship between active-site peptidomimetics and the West Nile virus (WNV) NS2B/NS3 serine protease. Our efforts lead to the discovery of a novel agmatine dipeptide inhibitor (compound 33, IC50 2.6 +/- 0.3 mu M) with improved inhibitory activity in comparison to the most potent inhibitor described in our recent report [IC50 4.7 +/- 1.2 mu M; Lim et al., Eur. J. Med. Chem. 46 (2011) 3130-3134]. In addition, our study cleared the contention surrounding the previous X-ray co-crystallization study and an enzyme inhibition report on the binding conformation adopted by active-site peptide aldehydes. Our data should provide valuable insights into the design of future peptidomimetic antivirals against WNV infections. (C) 2013 Elsevier Masson SAS. All rights reserved.
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