Fiche publication
Date publication
mars 2022
Journal
Molecules (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FRISCH Benoit
,
Dr LAVALLE Philippe
,
Dr KICHLER Antoine
Tous les auteurs :
Tallet L, Frisch E, Bornerie M, Medemblik C, Frisch B, Lavalle P, Guichard G, Douat C, Kichler A
Lien Pubmed
Résumé
There is an urgent need to develop new therapeutic strategies to fight the emergence of multidrug resistant bacteria. Many antimicrobial peptides (AMPs) have been identified and characterized, but clinical translation has been limited partly due to their structural instability and degradability in physiological environments. The use of unnatural backbones leading to foldamers can generate peptidomimetics with improved properties and conformational stability. We recently reported the successful design of urea-based eukaryotic cell-penetrating foldamers (CPFs). Since cell-penetrating peptides and AMPs generally share many common features, we prepared new sequences derived from CPFs by varying the distribution of histidine- and arginine-type residues at the surface of the oligourea helix, and evaluated their activity on both Gram-positive and Gram-negative bacteria as well as on fungi. In addition, we prepared and tested new amphiphilic block cofoldamers consisting of an oligourea and a peptide segment whereby polar and charged residues are located in the peptide segment and more hydrophobic residues in the oligourea segment. Several foldamer sequences were found to display potent antibacterial activities even in the presence of 50% serum. Importantly, we show that these urea-based foldamers also possess promising antifungal properties.
Mots clés
amphiphilic cationic foldamers, antibacterial activity, antifungal properties, oligourea-peptide hybrids, oligoureas
Référence
Molecules. 2022 Mar 7;27(5):
