Identification of a β3-peptide HIV fusion inhibitor with improved potency in live cells

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Bautista, Arjel D.¹  Stephens, Olen M.¹  Wang, Ligong³  Domaoal, Robert A.³  Anderson, Karen S.³  Schepartz, Alanna^1,2 

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA

关键词: Foldamer;    Peptidomimetic;    Anti-viral;    Drug design;   

DOI  :  10.1016/j.bmcl.2009.05.032

来源: Elsevier

【 摘 要 】

We recently reported a beta(3)-decapeptide, beta WWI-1, that binds a validated gp41 model in vitro and inhibits gp41-mediated fusion in cell culture. Here we report six analogs of beta WWI-1 containing a variety of non-natural side chains in place of the central tryptophan of the WWI-epitope. These analogs were compared on the basis of both gp41 affinity in vitro and fusion inibition in live, HIV-infected cells. One new beta(3)-peptide, beta WXI-a, offers a significantly improved CC50/EC50 ratio in the live cell assay. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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