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Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity
A K Marr1, S Cen2, R E W Hancock3
1Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada Division of Experimental Biology, Sidra Medical and Research Center, Outpatient Clinic, Doha, Qatar.
Abstract:
Leishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes ofLeishmania donovaniandLeishmania major We also report that theLeishmaniaprotease/virulence factor GP63 confers protection toLeishmaniafrom the cytolytic properties of alll-form peptides (E6, L-1018, and LL-37) but not thed-form peptide RI-1018. The results suggest that RI-1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy.
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