alexa Discovering high-affinity ligands for proteins: SAR by NMR.
Microbiology

Microbiology

Journal of Microbial & Biochemical Technology

Author(s): Shuker SB, Hajduk PJ, Meadows RP, Fesik SW

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Abstract 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.
This article was published in Science and referenced in Journal of Microbial & Biochemical Technology

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