Shuker S B, Hajduk P J, Meadows R P, Fesik S W
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Science. 1996 Nov 29;274(5292):1531-4. doi: 10.1126/science.274.5292.1531.
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.
本文描述了一种基于核磁共振（NMR）的方法，该方法可识别、优化与蛋白质近端亚位点结合的小有机分子，并将它们连接在一起以产生高亲和力配体。这种方法被称为“基于核磁共振的构效关系研究”（SAR by NMR），因为构效关系（SAR）是通过核磁共振获得的。利用该技术，通过连接两个具有微摩尔亲和力的配体，迅速发现了对FK506结合蛋白具有纳摩尔亲和力的化合物。该方法减少了发现高亲和力配体所需的化学合成量和时间，在靶向药物研究中似乎特别有用。
