Article

Projet
Conception, synthèse et étude de nouveaux hétérocycles azotés d'intérêts biologiques  
Martine DEMEUNYNCKIsabelle BAUSSANNE,   
Titre
Indolizine-based scaffolds as efficient and versatile scaffolds for drug target identification – Synthesis and study of biotin-tagged anti-angiogenic drugs  
Auteurs
Marie Arvin-Berod, Simon Bonte, Agnès Desroches-Castan, Sabine Brugière, Yohann Couté, Laurent Guyon, Jean-Jacques Feige, Isabelle Baussanne and Martine Demeunynck
Edition
ACS Omega, 2017, 2, 9221-9230
Année
2017
Résumé
We describe the synthesis of polyfunctional scaffolds based on a fluorescent indolizine core derivatized with various orthogonal groups. The scaffold was used to prepare drug-biotin conjugates that were then immobilized onto avidin-agarose for affinity chromatography. More specifically, the anti-angiogenic drug COB223, whose mechanism of action remained unclear, was chosen as a proof-of-concept drug. Separation of COB223-interacting proteins from human placental extracts unveiled unanticipated protein targets belonging to the family of regulatory RNA-binding proteins, which opens the way to new hypotheses on the mode of action of this anti-angiogenic drugs