|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 27, 24067-24072, July 5, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Institute of Life Sciences, The Hebrew University of
Jerusalem, Givat Ram 91904 Jerusalem, Israel
Antiplasmodial activity of the dermaseptin S4
derivative K4S4(1-13) (P) was shown to be mediated
by lysis of the host cells. To identify antiplasmodial peptides with
enhanced selectivity, we produced and screened new derivatives based on
P and singled out the aminoheptanoylated peptide (NC7-P) for its
improved antiplasmodial properties. Compared with P, NC7-P displayed
both increased antiparasitic efficiency and reduced hemolysis,
including against infected cells. Antiplasmodial activity of P and its
derivative was time-dependent and irreversible, implying a
cytotoxic effect. But, whereas the dose dependence of growth inhibition
and hemolysis of infected cells overlapped when treated with P, NC7-P
exerted more than 50% growth inhibition at peptide concentrations that
did not cause hemolysis. Noticeably, NC7-P but not P, dissipated
the parasite plasma membrane potential and caused depletion
of intraparasite potassium at nonhemolytic conditions. Confocal
microscopy analysis of infected cells localized the rhodaminated
derivative in association with parasite membranes and intraerythrocytic
tubulovesicular structures, whereas in normal cells, the peptide
localized exclusively at the plasma membrane. Overall, the data
demonstrate that antimicrobial peptides can be engineered to act
specifically on the membrane of intracellular parasites and support a
mechanism whereby NC7-P crosses the host cell plasma membrane and
disrupts the parasite membrane(s).
Direct Interaction of Dermaseptin S4 Aminoheptanoyl Derivative
with Intraerythrocytic Malaria Parasite Leading to Increased Specific
Antiparasitic Activity in Culture*
, and
*
This work was supported by Israel Science Foundation Grant
523/98.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biological
Chemistry, Inst. of Life Sciences, The Hebrew University of Jerusalem,
Givat Ram 91904 Jerusalem, Israel. E-mail:
hagai@vms.huji.ac.il.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. J. Mason, W. Moussaoui, T. Abdelrahman, A. Boukhari, P. Bertani, A. Marquette, P. Shooshtarizaheh, G. Moulay, N. Boehm, B. Guerold, et al. Structural Determinants of Antimicrobial and Antiplasmodial Activity and Selectivity in Histidine-rich Amphipathic Cationic Peptides J. Biol. Chem., January 2, 2009; 284(1): 119 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Radzishevsky, M. Krugliak, H. Ginsburg, and A. Mor Antiplasmodial Activity of Lauryl-Lysine Oligomers Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1753 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rotem, I. Radzishevsky, and A. Mor Physicochemical properties that enhance discriminative antibacterial activity of short dermaseptin derivatives. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Shalev, S. Rotem, A. Fish, and A. Mor Consequences of N-Acylation on Structure and Membrane Binding Properties of Dermaseptin Derivative K4-S4-(1-13) J. Biol. Chem., April 7, 2006; 281(14): 9432 - 9438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Rydlo, S. Rotem, and A. Mor Antibacterial Properties of Dermaseptin S4 Derivatives under Extreme Incubation Conditions Antimicrob. Agents Chemother., February 1, 2006; 50(2): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. VanCompernolle, R. J. Taylor, K. Oswald-Richter, J. Jiang, B. E. Youree, J. H. Bowie, M. J. Tyler, J. M. Conlon, D. Wade, C. Aiken, et al. Antimicrobial Peptides from Amphibian Skin Potently Inhibit Human Immunodeficiency Virus Infection and Transfer of Virus from Dendritic Cells to T Cells J. Virol., September 15, 2005; 79(18): 11598 - 11606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Radzishevsky, S. Rotem, F. Zaknoon, L. Gaidukov, A. Dagan, and A. Mor Effects of Acyl versus Aminoacyl Conjugation on the Properties of Antimicrobial Peptides Antimicrob. Agents Chemother., June 1, 2005; 49(6): 2412 - 2420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. EDA, S. EDA, and I. W. SHERMAN IDENTIFICATION OF PEPTIDES TARGETING THE SURFACE OF PLASMODIUM FALCIPARUM-INFECTED ERYTHROCYTES USING A PHAGE DISPLAY PEPTIDE LIBRARY Am J Trop Med Hyg, August 1, 2004; 71(2): 190 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Brand, J. R. S. A. Leite, L. P. Silva, S. Albuquerque, M. V. Prates, R. B. Azevedo, V. Carregaro, J. S. Silva, V. C. L. Sa, R. A. Brandao, et al. Dermaseptins from Phyllomedusa oreades and Phyllomedusa distincta. ANTI-TRYPANOSOMA CRUZI ACTIVITY WITHOUT CYTOTOXICITY TO MAMMALIAN CELLS J. Biol. Chem., December 13, 2002; 277(51): 49332 - 49340. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |