Discovering high-affinity ligands for proteins: SAR by NMR
Discovering high-affinity ligands for proteins: SAR by NMR
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DOI：
10.1126/science.274.5292.1531
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发表时间：
1996-11-29
期刊：
影响因子：
56.9
通讯作者：
Fesik, SW
中科院分区：
文献类型：
--
作者：
Shuker, SB;Hajduk, PJ;Fesik, SW
描述了一种基于核磁共振 (NMR) 的方法，其中识别、优化与蛋白质近端亚位点结合的有机小分子，并将其连接在一起以产生高亲和力配体。该方法称为“NMR SAR”，因为构效关系 (SAR) 是通过 NMR 获得的。利用这项技术，通过将两个具有微摩尔亲和力的配体连接起来，可以快速发现对 FK506 结合蛋白具有纳摩尔亲和力的化合物。该方法减少了化学合成的量和发现高亲和力配体所需的时间，并且在靶向药物研究中特别有用。
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called ''SAR by NMR'' because structure-activity relationships (SAR) are obtained from NMR. With this technique, compounds with nanomolar affinities for the FK506 binding protein were rapidly discovered by tethering two ligands with micromolar affinities. The method reduces the amount of chemical synthesis and time required for the discovery of high-affinity ligands and appears particularly useful in target-directed drug research.