Aminoquinoline–Rhodium(II) Conjugates as Src-Family SH3 Ligands
Aminoquinoline–Rhodium(II) Conjugates as Src-Family SH3 Ligands
复制标题
氨基喹啉与铑 (II) 缀合物作为 Src-Family SH3 配体
DOI：
10.1021/acsmedchemlett.9b00309
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发表时间：
2019
影响因子：
4.2
通讯作者：
Ball, Zachary T.
中科院分区：
文献类型：
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作者：
Martin, Samuel C.;Ball, Zachary T.
高亲和性、选择性配体被寻求用于各种生物分子，但在蛋白质-蛋白质相互作用空间中特别难以产生。铑（II）缀合物提供了一种基于结构的方法，以改善靶向蛋白质-蛋白质相互作用如SH 3结构域的亲和力和特异性。在这项研究中的小分子铑共轭物，我们报告了一个有效的ligand 4 b（Kd为27 nM）的林恩SH 3结构域的基础上，氨基喹啉片段。结果表明，基于特定的组氨酸相互作用，通过合作的无机-有机结合，即使是适度的小分子铅也可能获得强大的亲和力。对接研究揭示了结合的结构基础，并支持以前提出的结合模型。
High-affinity, selective ligands are sought for a variety of biomolecules but are particularly difficult to generate in the protein–protein interaction space. Rhodium(II) conjugates provide a structure-based approach to improved affinity and specificity for targeting protein–protein interactions such as SH3 domains. In this study of small-molecule–rhodium conjugates, we report a potent ligand4b(Kdof 27 nM) for the Lyn SH3 domain, based on an aminoquinoline fragment. The results demonstrate robust affinity gains possible from even modest small-molecule leads through cooperative inorganic–organic binding, based on specific histidine interactions. A docking study sheds light on the structural basis of binding and supports a previously proposed binding model.