Abstract
Addressing antimicrobial resistance by innovative drug design targeting protein degradation AntiMicrobial Resistance (AMR) represents one of the most challenging global Public Health issue, accounting for at least 1.2 M deaths worldwide, fuelled by a drying pipeline of antibiotics R&D; and the rapid diffusion of multidrug-resistant isolates. Meanwhile, the discovery of heterobifunctional molecules, able to recruit the eucaryotic proteasome to trigger the specific degradation of virtually any protein of interest (POI), has started a new era for medicinal chemistry. Such molecules, named PROTACs (PROteolysis-TArgeting Chimeras), already reached the stage of clinical development (e. g. androgen and estrogen receptor-targeting). Recent research demonstrated that protein targeted degradation can be achieved in Gram-positive bacteria, through the design of molecules bearing on one side a ligand of the POI and on the other a degron signal recognized by the ClpCP degradation machinery. Our project aims to reposition the PROTAC approach for the design of innovative and groundbreaking first-in-class compounds targeting protein degradation in Gram-negative bacteria, and therefore to establish proof of concept and feasibility of this promising approach, representing an interesting alternative to classical antibiotics.
Dettagli del progetto
Responsabile scientifico: Andrea Milelli
Strutture Unibo coinvolte:
Dipartimento di Scienze per la Qualità della Vita
Coordinatore:
Università degli Studi di TORINO(Italy)
Contributo totale Unibo: Euro (EUR) 70.570,00
Durata del progetto in mesi: 24
Data di inizio
30/11/2023
Data di fine:
28/02/2026
