Peptidic HIV integrase inhibitors derived from HIV gene products: Structure-activity relationship studies
Peptidic HIV integrase inhibitors derived from HIV gene products: Structure-activity relationship studies
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DOI：
10.1016/j.bmc.2010.07.050
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发表时间：
2010-09-15
影响因子：
3.5
通讯作者：
Tamamura, Hirokazu
中科院分区：
文献类型：
--
作者：
Suzuki, Shintaro;Maddali, Kasthuraiah;Tamamura, Hirokazu
对 HIV 整合酶 (IN) 抑制肽进行构效关系研究，该肽是通过筛选源自 HIV-1 基因产物的重叠肽库而发现的。由于位于 Vpr 第二螺旋的这些肽被认为具有 α 螺旋构象，因此将 Glu-Lys 对引入到 i 和 i + 4 位置以增加具有八精氨酰基的先导化合物的螺旋度。还对先导化合物进行了丙氨酸扫描，以鉴定负责抑制活性的氨基酸残基。结果表明α-螺旋结构对于表达抑制活性的重要性，并提出了整合酶和先导化合物的结合模型。 (C) 2010 Elsevier Ltd. 保留所有权利。
Structure-activity relationship studies were conducted on HIV integrase (IN) inhibitory peptides which were found by the screening of an overlapping peptide library derived from HIV-1 gene products. Since these peptides located in the second helix of Vpr are considered to have an alpha-helical conformation, Glu-Lys pairs were introduced into the i and i + 4 positions to increase the helicity of the lead compound possessing an octa-arginyl group. Ala-scan was also performed on the lead compound for the identification of the amino acid residues responsible for the inhibitory activity. The results indicated the importance of an a-helical structure for the expression of inhibitory activity, and presented a binding model of integrase and the lead compound. (C) 2010 Elsevier Ltd. All rights reserved.