| Discovering high-affinity ligands for proteins: SAR by NMR |
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| Author(s): Shuker SB, Hajduk PJ, Meadows RP, Fesik SW |
| Source: SCIENCE Volume: 274 Issue: 5292 Pages: 1531-1534 Published: NOV 29 1996 |
| Times Cited: 880 References: 22 |
| 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. ABBOTT LABS, DIV PHARMACEUT DISCOVERY, ABBOTT PK, IL 60064 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: VV775 |
| ISSN: 0036-8075 |