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Accueil > Animation Scientifique > Année 2014

Conférence Pr. Nicolas Moitessier

Mercredi 9 juillet 2014, 14h30, Salle Jean Barriol, Vandoeuvre-lès-Nancy.
Developing covalent and non covalent prolyl oligopeptidase inhibitors using a combination of biophysical, computational, biochemical and chemical approaches".
Pr. Nicolas Moitessier
Department of Chemistry, McGill University, Canada.

Résumé
Prolyl oligopeptidase (POP) was discovered in the mid-70’s and its high concentration in the central nervous system (CNS) immediately drew attention. Quickly POP was associated with cognitive functions through its neuropeptidase activity. Recently, a second wave of interest in the development of POP inhibitors has arisen and their potential in Alzheimer’s disease and Parkinson’s disease further investigated. Many of the reported POP inhibitors feature a reactive group such as a boronic acid, an aldehyde or a nitrile that reacts with the catalytic serine of POP to form a covalent bond. Covalent drugs can be extremely effective and profitable pharmaceuticals, yet they had been all but ignored in structure-based drug design campaigns. Until recently, concerns about their potential off-target reactivity and toxicity have often been raised. Recently, a significant shift in medicinal chemists’ opinion about covalent drugs has been observed. In fact, there are many examples of covalent drugs including three of the ten most widely prescribed medications in the U.S. as well as several common drugs including aspirin and penicillin. The advantages of covalent drugs are becoming increasingly recognized : they have extremely high potencies, long residence times (slow off-rates) and high levels of specificity. We will present our efforts towards the development of methods for the discovery of covalent and non covalent drugs and their application to the development of POP inhibitors.