Design of protease-resistant pexiganan enhances antileishmanial activity

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.