Isolation of a peptide containing d-amino acid residues that inhibits the α-helix-mediated p53-MDM2 interaction from a one-bead one-compound library
Isolation of a peptide containing d-amino acid residues that inhibits the α-helix-mediated p53-MDM2 interaction from a one-bead one-compound library
复制标题
从单珠单化合物文库中分离出含有 d-氨基酸残基的肽，该肽可抑制 α-螺旋介导的 p53-MDM2 相互作用
DOI：
10.1016/j.bmcl.2018.01.001
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发表时间：
2018
影响因子：
2.7
通讯作者：
Sando Shinsuke
中科院分区：
文献类型：
--
作者：
Morimoto Jumpei;Hosono Yuki;Sando Shinsuke
α-螺旋介导的蛋白质-蛋白质相互作用（PPI）是生物学研究和药物开发中的重要靶点。含α-氨基酸残基的肽具有广泛的表面积和较高的蛋白酶抗性，是抑制α-螺旋介导的PPI的理想分子。在这项研究中，使用一个珠子一个化合物的格式构建了一个肽库，旨在分离左手α-螺旋肽，这是有前途的分子作为α-螺旋介导的PPI的抑制剂。针对MDM 2和p53之间的α-螺旋介导的PPI筛选文库产生PPI的抑制剂。介绍了该库的设计和筛选，以及所发现肽的生化和光谱研究。
α-Helix-mediated protein–protein interactions (PPIs) are important targets in biological research and drug development. Peptides containingd-amino acid residues are attractive molecules for inhibiting α-helix-mediated PPIs because of their wide surface area and high protease resistance. In this study, a peptide library was constructed using a one-bead one-compound format designed to isolate left-handed α-helical peptides, which are promising molecules as inhibitors of α-helix-mediated PPIs. Screening of the library against an α-helix-mediated PPI between MDM2 and p53 yielded an inhibitor of the PPI. Design and screening of the library, and biochemical and spectroscopic studies of the discovered peptide are presented.