Tethering: fragment-based drug discovery.

Daniel A Erlanson; James A Wells; Andrew C Braisted

doi:10.1146/annurev.biophys.33.110502.140409

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Tethering: fragment-based drug discovery.

Daniel A Erlanson·James A Wells·Andrew C Braisted

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Abstract

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, Tethering1, 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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Binding Sites Drug Design Peptide Fragments Protein Array Analysis Protein Binding Protein Interaction Mapping Proteins Journal Article Research Support, Non-U.S. Gov't Review

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Daniel A Erlanson, James A Wells, Andrew C Braisted. 2004. Tethering: fragment-based drug discovery.. https://doi.org/10.1146/annurev.biophys.33.110502.140409

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