This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.01288-06v1 51/5/1753    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Radzishevsky, I. Articles by Mor, A. Search for Related Content PubMed PubMed Citation Articles by Radzishevsky, I. Articles by Mor, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2007, p. 1753-1759, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01288-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Antiplasmodial Activity of Lauryl-Lysine Oligomers

Department of Biotechnology & Food Engineering, Laboratory of Antimicrobial Peptides Investigation (LAPI), Technion—Israel Institute of Technology, Haifa, Israel,¹ Department of Biological Chemistry, Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel²

Received 15 October 2006/ Returned for modification 13 December 2006/ Accepted 11 February 2007

The ever evolving resistance of the most virulent malaria parasite, Plasmodium falciparum, to antimalarials necessitates the continuous development of new drugs. Our previous analysis of the antimalarial activities of the hemolytic antimicrobial peptides dermaseptins and their acylated derivatives implicated the importance of hydrophobicity and charge for drug action. Following these findings, an oligoacyllysine (OAK) tetramer designed to mimic the characteristics of dermaseptin was synthesized and assessed for its antimalarial activity in cultures of P. falciparum. The tetramer inhibited the growth of different plasmodial strains at low micromolar concentrations (mean 50% inhibitory concentration [IC₅₀], 1.8 µM). A structure-activity relationship study involving eight derivatives unraveled smaller, more potent OAK analogs (IC₅₀s, 0.08 to 0.14 µM). The most potent analogs were the most selective, with selectivity ratios of 3 orders of magnitude. Selectivity was strongly influenced by the self-assembly properties resulting from interactions between hydrophobic OAKs, as has been observed with conventional antimicrobial peptides. Further investigations performed with a representative OAK revealed that the ring and trophozoite stages of the parasite developmental cycle were equally sensitive to the compound. A shortcoming of the tested compound was the need for long incubation times in order for it to exert its full effect. Nevertheless, the encouraging results obtained in this study regarding the efficiency and selectivity of some compounds establish them as leads for further development.

Published ahead of print on 16 February 2007.

This article has been cited by other articles:

• Rotem, S., Radzishevsky, I. S., Bourdetsky, D., Navon-Venezia, S., Carmeli, Y., Mor, A. (2008). Analogous oligo-acyl-lysines with distinct antibacterial mechanisms. FASEB J. 22: 2652-2661 [Abstract] [Full Text]