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

Shuker SB, Hajduk PJ, Meadows RP, Fesik SW
Science. 1996 274 (5292): 1531-4

PMID: 8929414 · 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.

MeSH Terms (12)

Anilides Binding Sites Carrier Proteins DNA-Binding Proteins Heat-Shock Proteins Ligands Magnetic Resonance Spectroscopy Models, Molecular Proteins Structure-Activity Relationship Tacrolimus Tacrolimus Binding Proteins

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