Quantitative ranking of transient ligand binding to target...

Details Quantitative ranking of transient ligand binding to target... Quantitative ranking of transient ligand binding to target...

G - Physics

01

R

G01R 33/46 (2006.01) A61K 49/06 (2006.01) G01N 24/08 (2006.01) G01R 33/465 (2006.01)

Patent

CA 2472193

There is provided a method of quantitatively ranking transient ligand binding to target biomolecules by means of NMR relaxation dispersion profiles. The present invention also relates to a method to identify ligand site obeying two- state and more complex binding behavior in a transient complex of a ligand with a target molecule, still with the use of NMR. There is also provided an efficient method to quantitate fast dissociation rates of ligands containing at least one magnetic nuclei by performing NMR relaxation dispersion experiments at different protein concentrations, enabling the evaluation of populations and exchange rates, and extending the practical applicability of the NMR relaxation dispersion experiments.

Cette invention concerne l'utilisation de la résonance magnétique nucléaire pour classer de manière quantitative un ligand transitoire se liant à des biomolécules cibles. Cette invention concerne également un nouveau procédé permettant d'identifier un site de ligand obéissant à un comportement de liaison d'un complexe à deux états ou plus dans un complexe transitoire composé d'un ligand et d'une molécule cible, toujours à l'aide de la résonance magnétique nucléaire. Cette invention concerne également un procédé efficace permettant de quantifier les vitesses de dissociation de ligands contenant au moins un noyau magnétique au moyen d'expériences de dispersion par relaxation RMN à différents taux de concentration de protéine, ce qui permet d'évaluer les populations et les vitesses d'échange et d'élargir les possibilités d'application pratique des expériences de dispersion par relaxation RMN.

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