TY - JOUR
T1 - Protein-Observed Fluorine NMR
T2 - A Bioorthogonal Approach for Small Molecule Discovery
AU - Arntson, Keith E.
AU - Pomerantz, William C.K.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2016/6/9
Y1 - 2016/6/9
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jmedchem.5b01447
DO - 10.1021/acs.jmedchem.5b01447
M3 - Review article
C2 - 26599421
AN - SCOPUS:84974626866
SN - 0022-2623
VL - 59
SP - 5158
EP - 5171
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 11
ER -