title: Design of protease-resistant pexiganan enhances  antileishmanial activity.
abstract: Antimicrobial peptides are increasingly being explored as alternative agents for therapy against the parasitic protozoan Leishmania. Previously, we reported that the synthetic magainin analog, pexiganan, induced apoptosis of surface protease-deficient Leishmania. Here, we report the development of an arginine-rich variant of this peptide which has reduced protease susceptibility and enhanced activity against wild type Leishmania in vitro. This peptide induces calcium delocalization and caspase 3/7 activity indicative of apoptosis, demonstrating that structural modification of pexiganan leads to drastic changes in biologic activity against Leishmania.
authors.forename: Manjusha M
authors.initials: MM
authors.lastname: Kulkarni
authors.forename: Anna
authors.initials: A
authors.lastname: Karafova
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Bradford S
authors.initials: BS
authors.lastname: McGwire
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects*; D008969:Molecular Sequence Data; D021261:Parasitic Sensitivity Tests
chemical_list: D023181:Antimicrobial Cationic Peptides; D000981:Antiprotozoal Agents; D001120:Arginine; D020169:Caspases; D002118:Calcium; C093828:pexiganan