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DOCK程序。 用生化和酶的数据 这表明IN作为二聚体或更高阶的寡聚体，我们 选择了晶体中两个单体界面附近的位置 禽流感病毒的催化核心结构域（残基55-199）的结构 肉瘤病毒（ASV）IN. 该网站位于15埃从 活性位点。 使用DOCK程序，我们搜索了17万个分子， 可用化学品数据库（ACD）95.1中的小分子 可以绑定到这个网站的东西 从搜索中，30个分子 筛选，发现一种分子的IC 50为4 微摩尔。 从这个抑制剂中，我们使用相似性搜索来找到 另外5种抑制IN活性的分子，IC 50值小于 超过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.