Tethering: Fragment-based drug discovery

被引：298

作者：

Erlanson, DA ^{[1
]}

Wells, JA ^{[1
]}

Braisted, AC ^{[1
]}

机构：

[1] Sunesis Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE | 2004年 / 33卷

关键词：

disulfide exchange; small-molecule inhibitors; fragment assembly; structure-based drug design; molecular recognition;

D O I：

10.1146/annurev.biophys.33.110502.140409

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The genomics revolution has provided a deluge of new targets for drug discovery. To facilitate the drug discovery process, many researchers are turning to fragment-based approaches to find lead molecules more efficiently. One such method, Tethering(1), allows for the identification of small-molecule fragments that bind to specific regions of a protein target. These fragments can then be elaborated, combined with other molecules, or combined with one another to provide high-affinity drug leads. In this review we describe the background and theory behind Tethering and discuss its use in identifying novel inhibitors for protein targets including interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.

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页码：199 / 223

页数：29

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