Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
Bioorg Med Chem. 2010 Sep 15;18(18):6771-5. doi: 10.1016/j.bmc.2010.07.050. Epub 2010 Jul 25.
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 alpha-helical structure for the expression of inhibitory activity, and presented a binding model of integrase and the lead compound.
对通过筛选源自 HIV-1 基因产物的重叠肽文库发现的 HIV 整合酶(IN)抑制肽进行了构效关系研究。由于这些位于 Vpr 第二螺旋中的肽被认为具有α-螺旋构象,因此在具有八聚精氨酸基团的先导化合物的 i 和 i+4 位置引入了 Glu-Lys 对以增加其螺旋度。还对先导化合物进行了 Ala 扫描,以确定负责抑制活性的氨基酸残基。结果表明,对于抑制活性的表达,α-螺旋结构很重要,并提出了整合酶与先导化合物的结合模型。