Small-Molecule CD4-Mimics: Structure-Based Optimization of HIV-1 Entry Inhibition
Small-Molecule CD4-Mimics: Structure-Based Optimization of HIV-1 Entry Inhibition
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DOI：
10.1021/acsmedchemlett.5b00471
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发表时间：
2016-03-01
影响因子：
4.2
通讯作者：
Smith, Amos B., III
中科院分区：
文献类型：
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作者：
Melillo, Bruno;Liang, Shuaiyi;Smith, Amos B., III
基于计算、热力学和晶体学数据，对人免疫缺陷病毒（HIV）包膜糖蛋白gp 120的Phe 43空腔的一系列小分子配体进行了优化。重要的是，生物学评价显示，小分子CD 4模拟物（4-7）抑制HIV-1进入靶细胞的效力和中和宽度均显著高于先前的同类物，同时保持对靶病毒的高选择性。通过热力学和晶体学研究，其结合模式进行了表征。
The optimization, based on computational, thermodynamic, and crystallographic data, of a series of small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120 of human immunodeficiency virus (HIV) has been achieved. Importantly, biological evaluation revealed that the small-molecule CD4 mimics (4-7) inhibit HIV-1 entry into target cells with both significantly higher potency and neutralization breadth than previous congeners, while maintaining high selectivity for the target virus. Their binding mode was characterized via thermodynamic and crystallographic studies.