title: De novo cyclic pseudopeptides containing aza-β3-amino acids exhibiting antimicrobial activities.
abstract: De novo cyclic pseudopeptides composed of α-amino and aza-β(3)-amino acids were designed with the aim to obtain potential new antimicrobial agents. Antimicrobial cyclic pseudopeptides (ACPPs) are based on the properties of antimicrobial peptides (AMPs), so they are cationic and amphiphilic. Aza-β(3)-amino acids enhance the in vivo half-life of these compounds and offer the possibility to incorporate a large variety of side chains. Most of the 13 ACPPs exert antimicrobial activities in rich media with broad spectrum of antibacterial activities. Selectivity for bacterial over mammalian cells was determined by testing the hemolytic activities of ACPPs against sheep red blood cells (sRBC). We examined the ratio of cationic to hydrophobic residues as well as the type of hydrophobic side chains essential for biological activity of this class of ACPPs. These results will be useful for designing potential candidates for a therapeutic application.
authors.affiliation: Université de Rennes 1, ICMV, UMR CNRS 6226, 263 Av. du Général Leclerc, F-35042 Rennes Cedex, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Laurencin
authors.forename: Mosbah
authors.initials: M
authors.lastname: Amor
authors.forename: Yannick
authors.initials: Y
authors.lastname: Fleury
authors.forename: Michèle
authors.initials: M
authors.lastname: Baudy-Floc'h
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D009842:Oligopeptides; D010456:Peptides, Cyclic; D057786:Peptidomimetics