Open AccessMeasurement of Ligand–Target Residence Times by 1H Relaxation Dispersion NMR Spectroscopy
Author(s) -
Thomas Moschen,
Sarina Grutsch,
Michael Andreas Juen,
Christoph H. Wunderlich,
Christoph Kreutz,
Martin Tollinger
Publication year - 2016
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.6b01110
Subject(s) - chemistry , relaxation (psychology) , ligand (biochemistry) , nuclear magnetic resonance spectroscopy , millisecond , dispersion (optics) , nucleic acid , molecule , residence time (fluid dynamics) , kinetics , spectroscopy , small molecule , chemical physics , computational chemistry , analytical chemistry (journal) , stereochemistry , chromatography , organic chemistry , biochemistry , receptor , psychology , social psychology , physics , geotechnical engineering , quantum mechanics , astronomy , optics , engineering
A ligand-observed 1 H NMR relaxation experiment is introduced for measuring the binding kinetics of low-molecular-weight compounds to their biomolecular targets. We show that this approach, which does not require any isotope labeling, is applicable to ligand-target systems involving proteins and nucleic acids of variable molecular size. The experiment is particularly useful for the systematic investigation of low affinity molecules with residence times in the micro- to millisecond time regime.