建立一个基于配体的药效团模型来描绘 HIV-1 gp120 上的 CD4 结合部位，以鉴定新的 gp120-CD4 蛋白-蛋白相互作用抑制剂。
A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions.
机构信息
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi, 2, 53100 Siena, Italy.
出版信息
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6087-91. doi: 10.1016/j.bmcl.2009.09.029. Epub 2009 Sep 13.
A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infection, by direct interaction with gp120. Inactivity of compounds toward a M475I strain suggested specific contacts with the Phe43 cavity of gp120.
构建了一个基于 HIV-1 gp120 上 CD4 结合位点的动态靶标药效团模型，用于识别能够抑制 gp120-CD4 蛋白-蛋白相互作用的新化合物。两种化合物对细胞中的 HIV-1 复制具有微摩尔级别的抑制作用，这归因于它们通过与 gp120 的直接相互作用干扰了感染的进入步骤。化合物对 M475I 株的无活性表明其与 gp120 的 Phe43 腔有特异性结合。
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