MURYXIN
Vida saludable i prevenció de noves pandèmies
The disulfide bond as a chemical tool in cyclic peptide antibiotics: engineering disulfide polymyxins and murepavadin
The MURYXIN project introduces an innovative chemical approach to improve the performance of known cyclic peptide antibiotics, aiming to demonstrate that incorporating disulfide bonds improves the therapeutic window, specifically by reducing nephrotoxicity in antibiotics like polymyxins and murepavadin. The design preserves the overall antibiotic structure for antibacterial efficacy, while facilitating metabolization and detoxification in the kidney through disulfide bonds. The proof-of-concept plan involves synthesizing disulfide-polymyxins and murepavadin, formulation, conducting in vitro and in vivo assays to assess activity and low toxicity, estimating the therapeutic window, and exploring metabolites related to reductive opening for optimal metabolization and membrane-level mechanism of action. This approach may also be convenient to prevent accumulation of such antibiotics in the environment.
MURYXIN is a project of the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) and the European Comission, call 2022 - Disrupting drug resistance using innovative design.
