Titre : From Nitrone Cyclooctyne Cycloadditions to Activity-Based Protein Probes: Chemical Tools for Studying Living Systems.

Cette conférence sera prononcée (en anglais) par le Professeur John Pezacki, qui est à la fois chef de groupe de l'Institut Steacie des sciences moléculaires du Conseil national de recherches Canada (CRNC) et professeur auxiliaire aux départements de chimie et de Biochimie, microbiologie & immunologie de l'Université d'Ottawa.

Résumé : We have developed a number of tools for the discovery and characterization of biomolecular interactions including new methods in activity-based protein profiling, activity-based imaging, tools for cell surface labeling, and small molecule probes for investigating lipid metabolism and membrane alterations. Representative examples will be presented. Reactions that do not interfere with biological functionality, termed bioorthogonal, have emerged as powerful tools for the site specific modification of biomolecules in cells and within living organisms. We have developed several strategies based on strain promoted cycloadditions of cyclic nitrones with cyclooctynes for bioothogonal labeling of proteins. These reactions are among the fastest reported in the literature and have potential to be used in multiplex labeling as well. Reactions of a series of cyclic nitrones with biaryl-aza-cyclooctynone (BARAC) and bicyclo[6.1.0]nonyne (BCN) and their ability to probe biological systems will be presented. We have also developed a number of probes for activity-based protein profiling (ABPP), a technique which allows for the identification of differentially active enzymes in complex proteomic samples. Examples for the study of fatty acid synthase (FASN),  rhomboid proteins, and phosphatidylinositol kinases and their application in profiling studies will also be presented.  Taken together these studies will be used to illustrate new ways to track down the cellular and molecular details of how biological systems work, such as how the hepatitis C virus hijacks its host cells, discover new biomarkers, and new targets for therapeutic intervention.

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