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Drastic changes in the plasma membrane of Plasmodium falciparum-infected red blood cells (iRBCs) make the surface of iRBCs distinct from that of the uninfected erythrocyte. To identify small peptides that would specifically recognize the altered surface of iRBCs, we screened a phage display peptide library (PDL) on the surface of iRBCs. After the sixth panning of the PDL, eight phage clones of 18 sequenced clones had the same sequence, LVDAAAL (named P1) and specific binding of P1 to the surface of iRBCs was confirmed using phage expressing P1 peptides and synthetic P1 peptide. When P1 peptide was conjugated with a peptide having moderate hemolytic activity, the peptide conjugate inhibited the growth of intracellular parasites in a dose-dependent manner, whereas control peptides were without effect. Our results demonstrate that the P1 peptide may be a lead compound for the development of anti-malarial agents targeting the surface of iRBCs.
Received January 12, 2004. Accepted for publication March 17, 2004.
Acknowledgments: We thank Jacques Prudhomme for expert technical assistance. We also thank Dr. Renata Pasqualini for the generous gift of the phage display library used in this work.
Financial support: This work was supported by grant AI-43608 (to Irwin W. Sherman) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Shigetoshi Eda was supported by an Overseas Research Fellowship from the Japan Society for the Promotion of Sciences.
Authors addresses: Keiko Eda, Department of Pathobiology, University of Tennessee, Knoxville, TN 37996. Shigetoshi Eda, Department of Forestry, Wildlife and Fisheries, University of Tennessee, Knoxville, TN 37996. Irwin W. Sherman, Department of Biology, University of California, Riverside, CA 92521, Telephone: 909-787-5905, Fax: 909-787-4286, E-mail: sherman{at}mail.ucr.edu.
* These authors contributed equally to this work.
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