Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2018-2019).

NMX Research and Solutions (NMX) is a Canadian translational research organization that providesx000D
development for drug discovery, including medicinal chemistry for leads and biophysical screening for hits.x000D
The main biophysical strategies of NMX is nuclear magnetic resonance (NMR), which provides atomic-levelx000D
information about compound solution properties and interactions with target biomolecules. Over the last years,x000D
NMX has developed a unique toolbox of NMR strategies to ensure delivery of quality hits and leads. Thesex000D
NMR-based integrated strategies for ligand screening for drug discovery now need to be supported withx000D
state-of-the-art biophysical techniques. In this context, NMX has contacted Dr. Steve Bourgault to initiate ax000D
collaboration in order to support their innovative NMR methods for quantitative determination of smallx000D
molecule binding affinity and binding kinetics. The analytical biochemistry laboratory of Dr. Bourgault atx000D
UQÀM has developed over the last years an expertise in the biophysical analysis of biomolecular interactions,x000D
including isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR).x000D
In this project, we will develop SPR and ITC strategies in parallel with NMR-based fragment-based leadx000D
discovery strategies through the screening of small molecules to identify ligands of galectin-7.x000D
SPR and ITC are state-of-the-art techniques for studying molecular interactions and for measuring bindingx000D
affinity (Kd). However, the screening of the binding of low-molecular weight compounds, as used inx000D
fragment-based lead discovery strategies, is very challenging and requires innovative techniques and manyx000D
rounds of optimisation. Moreover, many drug targets self-assemble into oligomeric states (dimer, tetramer) inx000D
solution, as for galectin-7. This makes any attempts to correlate the results obtained from different biophysicalx000D
methods all but trivial. Using our expertise in the characterization of molecular interactions, we will supportx000D
NMX in the development of their unique NMR-based screening platform and we will gain a unique andx000D
unprecedented direct correlation between these biophysical techniques.