Design, synthèse et criblage de chimiothèques peptidomimétiques pour la découverte d'agents antinéoplasiques

Authors: Vézina-Dawod, Simon
Advisor: Biron, Éric
Abstract: Targeting protein-protein interactions represents an innovative and under-exploited therapeutic approach by the pharmaceutical industry and biomedical research. Because of their physicochemical nature, protein-protein interactions represent a major challenge for conventional screening methods with small molecule libraries. Indeed, the chemical space covered by the molecular structures found in the available libraries is poorly adapted to the reality of protein-protein interactions. In order to develop privileged and better adapted structures, the medicinal chemist must understand the nature of these interactions and move away from the traditional dogma of the so-called drug-like molecules. Peptides are excellent candidates for studying these interactions, nevertheless their pharmacological properties are generally disappointing in vivo. Peptidomimetism is then a more than relevant concept to combine the selectivity and efficiency of interaction against proteins with the concepts of bioavailability and metabolic stability. Many peptidomimetic platforms are available or emerging, and several major challenges are on the horizon. Indeed, the incorporation of a large molecular diversity and the adaptation of these platforms with the high throughput biological screening methods are only a few examples of the challenges that chemists and biochemists will have to meet. This work deals with the development and exploitation of different peptidomimetic molecular diversities, either macrocyclic or heterocyclic, but which serve the same purpose: to exploit privileged structures to discover new modulators of protein-protein interactions or simply innovative bioactive agents with advantageous pharmacological properties.
Document Type: Thèse de doctorat
Issue Date: 2018
Open Access Date: 24 April 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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