Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Whitby, Landon R.¹  Boyle, Kristopher E.¹  Cai, Lifeng²  Yu, Xiaoqian²  Gochin, Miriam²  Boger, Dale L.¹ 

[1] Scripps Res Inst, Dept Chem, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[2] Touro Univ Calif, Dept Basic Sci, Vallejo, CA 94592 USA

关键词: HIV;    gp41;    Fusion inhibitors;    alpha-Helix mimetics;   

DOI  :  10.1016/j.bmcl.2012.02.062

来源: Elsevier

【 摘 要 】

The evaluation of a comprehensive alpha-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR alpha-helix provided a detailed depiction of structural features required for binding and led to the discovery of small molecule inhibitors (K-i 0.6-1.3 mu M) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC50 5-8 mu M). (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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