Inorganic polyhedral metallacarborane inhibitors of HIV protease:: A new approach to overcoming antiviral resistance
Inorganic polyhedral metallacarborane inhibitors of HIV protease:: A new approach to overcoming antiviral resistance
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DOI：
10.1021/jm8002334
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发表时间：
2008-08-14
影响因子：
7.3
通讯作者：
Konvalinka, Jan
中科院分区：
文献类型：
--
作者：
Kozisek, Milan;Cigler, Petr;Konvalinka, Jan
HIV蛋白酶（PR）是合理的抗HIV药物设计的主要目标。我们之前已将二十面体金属碳硼烷鉴定为一类新型非肽蛋白酶抑制剂。现在我们证明，取代的金属碳硼烷是通过定点诱变制备或从 HIV 阳性患者克隆制备的耐药 HIV PR 的有效且特异性的竞争性抑制剂。分子模型通过非常规的结合模式解释了金属碳硼烷的抑制特性。
HIV protease (PR) is a prime target for rational anti-HIV drug design. We have previously identified icosahedral metallacarboranes as a novel class of nonpeptidic protease inhibitors. Now we show that substituted metallacarboranes are potent and specific competitive inhibitors of drug-resistant HIV PRs prepared either by site-directed mutagenesis or cloned from HIV-positive patients. Molecular modeling explains the inhibition profile of metallacarboranes by their unconventional binding mode.