INHIBITION OF HIV 1 INTEGRASE

我们已经确定了一类HIV-1整合酶(IN)抑制剂 使用对接程序。生化和酶的数据 这表明IN作为二聚体或更高阶低聚物，我们 选择晶体中两个单体界面附近的位置 禽类催化核心区(残基55-199)的结构 肉瘤病毒(Asv.)该网站位于15埃距离 活动站点。使用对接程序，我们搜索了17万个分子 在小分子可用化学品数据库(ACD)95.1中 可以绑定到这个站点。从搜索中，发现了30个分子 选择进行筛选，显示一个IC50为4的分子 微摩尔。从这个抑制物中，我们使用相似性搜索来找到 5个抑制IN活性的额外分子，其IC50值较低 大于5微摩尔。

We have identified a class of HIV-1 integrase (IN) inhibitors using the DOCK program. With biochemical and enzymatic data suggesting that IN acts as a dimer or higher-order oligomer, we selected a site near the interface of two monomers in the crystal structure of the catalytic core domain (residues 55-199) of Avian Sarcoma Virus (ASV) IN. The site is located 15 angstroms from the active sites. Using the DOCK program, we searched 170,000 molecules in the Available Chemicals Database (ACD) 95.1 for small molecules that could bind to this site. From the search, 30 molecules were selected for screening, revealing one molecule with an IC50 of 4 micromolar. From this inhibitor, we used similarity searching to find 5 additional molecules that inhibit IN activity with IC50 values less than 5 micromolar.