NMR fragment screening: Tackling protein-protein interaction targets

作者：Schade M^*; Oschkinat H

来源：Current Opinion in Drug Discovery & Development, 2005, 8(3): 365-373.

• drug discovery
• fragment-based lead discovery
• high-throughput screening
• NMR screening
• PDZ domains
• protein-protein interactions

High-throughput screening of libraries containing compounds of 'drug-like' molecular weight has frequently resulted in no or poor drug candidates, especially when screening against demanding drug targets such as protein-protein interactions. Fragment-based lead discovery and optimization has evolved as a promising solution to this problem by combining the universal adaptability of low-molecular-weight fragments with immediate structural information on fragment binding modes. This review focuses on nuclear magnetic resonance (NMR) fragment screening techniques, which provide a unique combination of medium-throughput, direct binding site information and broad applicability. The utility and exemplary data of chemical shift-detected NMR fragment screening applied to the challenging protein-protein interaction target PDZ domains are summarized.

• 出版日期2005-5