Footprint-based identification of viral entry inhibitors targeting HIVgp41

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Holden, Patrick M.¹  Kaur, Harmeet²  Goyal, Rashi³  Gochin, Miriam^2,4  Rizzo, Robert C.^1,5 

[1] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA

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

[3] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA

[4] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA

[5] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA

关键词: HIVgp41;    Virtual screening;    Structure-based drug design;    Molecular footprints;    Pose rescoring;    Docking;    DOCK;   

DOI  :  10.1016/j.bmcl.2012.02.017

来源: Elsevier

【 摘 要 】

A targeted virtual screen to the N-helix hydrophobic pocket on HIVgp41 was performed using DOCK followed by re-ranking with a new footprint-based scoring function which employed native gp41 C-helix residues as a reference. Of ca. 500,000 small molecules screened, 115 were purchased, and 7 hits were identified with favorable binding (K-i), cell-cell fusion (IC50), and cytotoxicity (CC50) profiles. Three of the seven active compounds would not have been discovered without the use of the footprints, demonstrating the utility of the method for structure-based design when a known reference compound or substrate is available. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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