How to MOdulate the SAlt-stability of antimicRobial DEFensins – MOSAR-DEF

The preclinical development of cationic antimicrobial peptides as an alternative to antibiotics is precluded, among other processes, by their inactivation by salts. Taking inspiration from marine biodiversity, our goal is to turn salt-sensitive human defensins into salt-stable defensins. This ambitious goal is made possible thanks to (i) recent discoveries from our consortium on the structure/activity of big-defensins, the marine ancestors of vertebrate ß-defensins (ii) new methodologies in chemical synthesis and engineering of such molecules, and (iii) the multidisciplinary team gathered in the MOSAR-Def consortium that brings together peptide chemists, biochemists, structural biologists, microbiologists (marine and human) and cell physiolgists. The project will contribute to significant knowledge on the mechanisms of defensins active both at normal and high salt concentrations, and their therapeutic applications. This represents a step further to unravel alternatives to conventional antibiotics treatments.