2° SEMINARIO QUÍMICA ORGÁNICA IQUIR 2021

SEMINARIO QUÍMICA ORGÁNICA 12-04-21

EXPOSITOR: Dra. Noelia Medrán

TÍTULO: "Peptidomimetic toolbox for drug discovery. Local modifications, global restrictions"

FUENTE: (a) Elena Lenci and Andrea Trabocchi, "Peptidomimetic toolbox for drug discovery", Chem. Soc. Rev., 2020, 49, 3262-3277. (b) Adam P. Treder, Jennifer L. Hickey, Marie-Claude J. Tremblay, Serge Zaretsky, Conor C. G. Scully, John Mancuso, Annie Doucet, Andrei K. Yudin, and Eric Marsault, "Solid‐Phase Parallel Synthesis of Functionalised Medium‐to‐Large Cyclic Peptidomimetics through Three‐Component Coupling Driven by Aziridine Aldehyde Dimers", Chem. Eur. J. 2015, 21, 9249-9255.

DÍA, HORA y LUGAR: Lunes 12 de abril de 2021, 18:00 h, Plataforma MEET GOOGLE.

Link: meet.google.com/bfh-poxv-bso

RESUMEN: (a) The art of transforming peptides into drug leads is still a dynamic and fertile field in medicinal chemistry and drug discovery. Peptidomimetics can respond to peptide limitations by displaying higher metabolic stability, good bioavailability and enhanced receptor affinity and selectivity. Various synthetic strategies have been developed over the years in order to modulate the conformational flexibility and the peptide character of peptidomimetic compounds. This tutorial review aims to outline useful tools towards peptidomimetic design, spanning from local modifications, global restrictions and the use of secondary structure mimetics. Selected successful examples of each approach are presented to document the relevance of peptidomimetics in drug discovery. (b) The first solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.