Development of anti-HIV peptides based on a viral capsid protein
Development of anti-HIV peptides based on a viral capsid protein
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DOI：
10.1002/bip.22920
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发表时间：
2017-01-01
期刊：
影响因子：
2.9
通讯作者：
Tamamura, Hirokazu
中科院分区：
文献类型：
--
作者：
Mizuguchi, Takaaki;Ohashi, Nami;Tamamura, Hirokazu
针对HIV-1衣壳（CA）蛋白的具有细胞渗透性的肽抑制剂可能通过调节HIV-1复制来治疗。已经合成了覆盖HIV-1 CA蛋白的整个序列的重叠片段肽文库，其中添加了八-乙酰基部分以增加其细胞渗透性。在这些肽中，已经发现了几种抑制HIV-1复制周期的化合物。在基于细胞的抗HIV测定中，将细胞穿透功能如八-乙酰基结合到单个肽上并加入氯喹，以前被证明是一种有用的测定方法，用于寻找活性肽。在氯喹存在或不存在的情况下进行了抗HIV测定，发现大多数化合物在存在氯喹的情况下比在不存在氯喹的情况下具有更高的抗HIV活性。一些有效的抗HIV药物种子可能天然地隐藏在CA蛋白中，并可能成为HIV抑制剂的有用线索。
Peptide inhibitors with cell permeability targeting an HIV-1 capsid (CA) protein might make therapeutic by regulating HIV-1 replication. Overlapping fragment peptide libraries covering the whole sequence of an HIV-1 CA protein have been synthesized with the addition of an octa-arginyl moiety to increase their cell permeability. Amongst these peptides, several compounds which inhibit the HIV-1 replication cycle have been found. Conjugation of cell-penetrating functions such as an octa-arginyl group to individual peptides in combination with the addition of chloroquine in cell-based anti-HIV assays was previously proven to be a useful assay method with which to search for active peptides. Anti-HIV assays have been performed in the presence or absence of chloroquine and found that most of compounds have higher anti-HIV activity in the presence, rather than in the absence of chloroquine. Some potent seeds as anti-HIV agents might naturally lie hidden in CA proteins, and could become useful leads to HIV inhibitors.