Description : The THERAPEPTICS project proposes to implement an original methodology based on polymer chemistry to synthesize new macromolecules made of amino-acids, as AMP simplified analogues, by the polymerization of dedicated NCAs, in order to target Clostridium difficile. To improve polymer resistance toward proteases, we propose to synthesize N-alkylated NCA, an innovative design that may permit the oral use of these polymers. We propose to conduct a rigorous and extensive study of the physico-chemical parameters (polymer size, H/C ratio, nature of amino-acids, N-alkylation…) allowing antibacterial activity and narrow spectrum of action, to access to structure-activity relationships and try to establish a macromolecular pharmacophore. The comparative evaluation of the biological profile of linear polymers, versus macrocyclic ones, will also be studied, in order to design optimal polymers with a high resistance toward proteases along with a poor enteric absorption, to avoid systemic toxicity.
Funding : CoNaCyT
Partner : Institut Pasteur, CNRS UMR 2001, Pathogenesis of Bacterial Anaerobes