title: Development of novel membrane active lipidated peptidomimetics active against drug resistant clinical isolates.
abstract: A new series of small cationic lipidated peptidomimetics have been synthesized and found to be highly active against several susceptible as well as drug resistant clinical isolates of bacteria and fungi. All lipidated peptidomimetics do not cause significant lysis of human erythrocytes (HC50>200μg/mL). Calcein dye leakage experiment revealed membranolytic effect of LPEP08 which was further confirmed by scanning electron microscopy (SEM). The involvement of intracellular targets as an alternate mode of action was precluded by DNA retardation assay. Additionally, LPEP08 exhibit high proteolytic stability and dose not elicit resistance against drug resistant clinical isolate of Staphylococcusaureus, even after 16 rounds of passaging. These results demonstrate the potential of lipidated peptidomimetics as biocompatible anti-infective therapeutics.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Solan 173234, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Lohan
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Solan 173234, India.
authors.forename: Arneesh
authors.initials: A
authors.lastname: Kalanta
authors.affiliation: Environmental Biotechnology & Microbial Biochemistry, Institute of Microbial Technology, Chandigarh 160036, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sonkusre
authors.affiliation: Environmental Biotechnology & Microbial Biochemistry, Institute of Microbial Technology, Chandigarh 160036, India.
authors.forename: Swaranjit Singh
authors.initials: SS
authors.lastname: Cameotra
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Solan 173234, India. Electronic address: bishtchem2005@gmail.com.
authors.forename: Gopal Singh
authors.initials: GS
authors.lastname: Bisht
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D025141:Drug Resistance, Fungal / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D057786:Peptidomimetics
keywords: Antimicrobial peptides; Drug resistance; Lipopeptides; Membranolytic; Peptidomimetics