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

Keith E. Arntson, William C.K. Pomerantz

Research output: Contribution to journalReview articlepeer-review

127 Scopus citations


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
Issue number11
StatePublished - Jun 9 2016

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.


Dive into the research topics of 'Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery'. Together they form a unique fingerprint.

Cite this