Titre : Advances in Peptide Macrocyclization.
Endroit : Pavillon Roger-Gaudry, salle G-815 à 11 h.
Hôte : Professeur William Lubell.
La conférence sera prononcée (en anglais) par le professeur Andrei Yudin, du Département de chimie de l'University of Toronto.
Résumé : Macrocycles are a class of molecules that continue to attract attention as therapeutic agents and chemical probes. We have developed a synthetic chemistry platform that allows us to streamline the discovery and development of bioactive macrocycles. While this class of molecules is promising, it does present challenges that are atypical for small molecule drugs. The main issue is that the structural properties responsible for cellular permeability of macrocycles are not correlated with those that are responsible for target engagement. We have identified some emerging principles that govern the behavior of peptide macrocycles obtained through the use of aziridine aldehydes. In addition, we recently discovered a macrocyclization reaction that results in the installation of unsaturated heterocycles within the large ring frameworks. In this lecture, I will illuminate our ongoing studies aimed at the design of integrin inhibitors and will discuss some counterintuitive findings that were made when we attempted to control over cellular permeability. The main lesson is that well-behaved structure-activity relationships are less likely for macrocycles when compared to small molecules. This lack of predictability will continue to fuel this area of research for many years.
