19F-NMR in Target-based Drug Discovery

Author(s): CongBao Kang* .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 26 , 2019

Abstract:

Solution NMR spectroscopy plays important roles in understanding protein structures, dynamics and protein-protein/ligand interactions. In a target-based drug discovery project, NMR can serve an important function in hit identification and lead optimization. Fluorine is a valuable probe for evaluating protein conformational changes and protein-ligand interactions. Accumulated studies demonstrate that 19F-NMR can play important roles in fragment- based drug discovery (FBDD) and probing protein-ligand interactions. This review summarizes the application of 19F-NMR in understanding protein-ligand interactions and drug discovery. Several examples are included to show the roles of 19F-NMR in confirming identified hits/leads in the drug discovery process. In addition to identifying hits from fluorinecontaining compound libraries, 19F-NMR will play an important role in drug discovery by providing a fast and robust way in novel hit identification. This technique can be used for ranking compounds with different binding affinities and is particularly useful for screening competitive compounds when a reference ligand is available.

Keywords: 19F NMR, drug discovery, protein structure, hit to lead, hit identification, protein-ligand interactions.

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Article Details

VOLUME: 26
ISSUE: 26
Year: 2019
Page: [4964 - 4983]
Pages: 20
DOI: 10.2174/0929867326666190610160534
Price: $95

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