Table of Contents
Molecular Biology International
Volume 2011 (2011), Article ID 854626, 10 pages
http://dx.doi.org/10.4061/2011/854626
Research Article

Peptide Inhibition of Topoisomerase IB from Plasmodium falciparum

1Department of Molecular Biology and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, C.F. Møllers Allé 3, Building 1130, 8000 Aarhus C, Denmark
2Department of Biology and Center of Biostatistics and Bioinformatics, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133 Rome, Italy
3Interuniversity Consortium, National Institute Biostructure and Biosystems (I.N.B.B.), 00136 Rome, Italy

Received 1 December 2010; Accepted 3 March 2011

Academic Editor: Hemanta K. Majumder

Copyright © 2011 Amit Roy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Control of diseases inflicted by protozoan parasites such as Leishmania, Trypanosoma, and Plasmodium, which pose a serious threat to human health worldwide, depends on a rather small number of antiparasite drugs, of which many are toxic and/or inefficient. Moreover, the increasing occurrence of drug-resistant parasites emphasizes the need for new and effective antiprotozoan drugs. In the current study, we describe a synthetic peptide, WRWYCRCK, with inhibitory effect on the essential enzyme topoisomerase I from the malaria-causing parasite Plasmodium falciparum. The peptide inhibits specifically the transition from noncovalent to covalent DNA binding of P. falciparum topoisomerase I, while it does not affect the ligation step of catalysis. A mechanistic explanation for this inhibition is provided by molecular docking analyses. Taken together the presented results suggest that synthetic peptides may represent a new class of potential antiprotozoan drugs.