利用综合 α-螺旋模拟文库发现针对 gp41 的 HIV 融合抑制剂。
Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library.
机构信息
Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
出版信息
Bioorg Med Chem Lett. 2012 Apr 15;22(8):2861-5. doi: 10.1016/j.bmcl.2012.02.062. Epub 2012 Mar 3.
Abstract
The evaluation of a comprehensive α-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR α-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 μM) 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 (IC(50) 5-8 μM).
摘要
对一个全面的α-螺旋模拟文库进行评估，以结合 gp41 NHR 疏水性口袋识别分子内 CHR α-螺旋，提供了对结合所需结构特征的详细描述，并导致发现了小分子抑制剂（Ki 为 0.6-1.3 μM），这些抑制剂不仅与过去十年中披露的那些具有相同或更高的效力，而且在细胞-细胞融合测定中也具有有效的活性（IC50 为 5-8 μM）。
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