Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery

Keith E. Arntson, William C.K. Pomerantz

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

The 19F isotope is 100% naturally abundant and is the second most sensitive and stable NMR-active nucleus. Unlike the ubiquitous hydrogen atom, fluorine is nearly absent in biological systems, making it a unique bioorthogonal atom for probing molecular interactions in biology. Over 73 fluorinated proteins have been studied by 19F NMR since the seminal studies of Hull and Sykes in 1974. With advances in cryoprobe production and fluorinated amino acid incorporation strategies, protein-based 19F NMR offers opportunities to the medicinal chemist for characterizing and ultimately discovering new small molecule protein ligands. This review will highlight new advances using 19F NMR for characterizing small molecule interactions with both small and large proteins as well as detailing NMR resonance assignment challenges and amino acid incorporation approaches.

Original languageEnglish (US)
Pages (from-to)5158-5171
Number of pages14
JournalJournal of Medicinal Chemistry
Volume59
Issue number11
DOIs
StatePublished - Jun 9 2016

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