Volume 71, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Drastic changes in the plasma membrane of -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.


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  1. Trigg P, Kondrachine A, 1998. The current global malaria situation. Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press, 11–22.
  2. Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2 : 209–218.
  3. Frevert U, Andrea C, 1998. Invasion of vertebrate cells: hepatocytes. Sherman IW, ed. Malaria: arasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press, 73–91.
  4. Barnwell JW, Galinski MR, 1998. Invasion of vertebrate cells: erythrocytes. Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press, 93–120.
  5. Cowman AF, 1998. The molecular basis of resistance to the sulfones, sulfonamides, and dihydrofolate reductase inhibitors. Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press, 317–330.
  6. Vaidya AB, 1998. Mitochondrial physiology as a target for atovaquone and other antimalarials. Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press, 355–368.
  7. Aikawa M, Rabbege JR, Udeinya I, Miller LH, 1983. Electron microscopy of knobs in Plasmodium falciparum-infected erythrocytes. J Parasitol 69 : 435–437.
  8. Nagao E, Kaneko O, Dvorak JA, 2000. Plasmodium falciparum-infected erythrocytes: qualitative and quantitative analyses of parasite-induced knobs by atomic force microscopy. J Struct Biol 130 : 34–44.
  9. Maguire PA, Sherman IW, 1990. Phospholipid composition, cholesterol content and cholesterol exchange in Plasmodium falciparum-infected red cells. Mol Biochem Parasitol 38 : 105–112.
  10. Eda S, Sherman IW, 2002. Cytoadherence of malaria-infected red blood cells involves exposure of phosphatidylserine. Cell Physiol Biochem 12 : 373–384.
  11. Maguire PA, Prudhomme J, Sherman IW, 1991. Alterations in erythrocyte membrane phospholipid organization due to the intracellular growth of the human malaria parasite, Plasmodium falciparum. Parasitology 102 : 179–186.
  12. Brand VB, Sandu CD, Duranton C, Tanneur V, Lang KS, Huber SM, Lang F, 2003. Dependence of Plasmodium falciparum in vitro growth on the cation permeability of the human host erythrocyte. Cell Physiol Biochem 13 : 347–356.
  13. Smith JD, Gamain B, Baruch DI, Kyes S, 2001. Decoding the language of var genes and Plasmodium falciparum sequestration. Trends Parasitol 17 : 538–545.
  14. Winograd E, Sherman IW, 1989. Naturally occurring anti-band 3 autoantibodies recognize a high molecular weight protein on the surface of Plasmodium falciparum infected erythrocytes.Biochem Biophys Res Commun 160 : 1357–1363.
  15. Winograd E, Sherman IW, 1989. Characterization of a modified red cell membrane protein expressed on erythrocytes infected with the human malaria parasite Plasmodium falciparum: possible role as a cytoadherent mediating protein. J Cell Biol 108 : 23–30.
  16. Willats WG, 2002. Phage display: practicalities and prospects. Plant Mol Biol 50 : 837–854.
  17. Samoylova TI, Ahmed BY, Vodyanoy V, Morrison NE, Samoylov AM, Globa LP, Baker HJ, Cox NR, 2002. Targeting peptides for microglia identified via phage display. J Neuroimmunol 127 : 13–21.
  18. Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do KA, Logothetis CJ, Pasqualini R, 2002. Steps toward mapping the human vasculature by phage display. Nat Med 8 : 121–127.
  19. da Silva A Jr, Kawazoe U, Freitas FF, Gatti MS, Dolder H, Schumacher RI, Juliano MA, da Silva MJ, Leite A, 2002. Avian anticoccidial activity of a novel membrane-interactive peptide selected from phage display libraries. Mol Biochem Parasitol 120 : 53–60.
  20. Nicklin SA, White SJ, Watkins SJ, Hawkins RE, Baker AH, 2000. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation 102 : 231–237.
  21. Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193 : 673–675.
  22. Pasvol G, Wilson RJ, Smalley ME, Brown J, 1978. Separation of viable schizont-infected red cells of Plasmodium falciparum from human blood. Ann Trop Med Parasitol 72 : 87–88.
  23. Lambros C, Vanderberg JP, 1979. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 65 : 418–420.
  24. Koivunen E, Gay DA, Ruoslahti E, 1993. Selection of peptides binding to the alpha 5 beta 1 integrin from phage display library. J Biol Chem 268 : 20205–20210.
  25. Scott JK, Smith GP, 1990. Searching for peptide ligands with an epitope library. Science 249 : 386–390.
  26. Prudhomme JG, Sherman IW, 1999. A high capacity in vitro assay for measuring the cytoadherence of Plasmodium falci parum-infected erythrocytes. J Immunol Methods 229 : 169–176.
  27. Dathe M, Wieprecht T, 1999. Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. Biochim Biophys Acta 1462 : 71–87.
  28. Javadpour MM, Juban MM, Lo WC, Bishop SM, Alberty JB, Cowell SM, Becker CL, McLaughlin ML, 1996. De novo antimicrobial peptides with low mammalian cell toxicity. J Med Chem 39 : 3107–3113.
  29. Baruch DI, Rogerson SJ, Cooke BM, 2002. Asexual blood stages of malaria antigens: cytoadherence. Chem Immunol 80 : 144–162.
  30. Strahilevitz J, Mor A, Nicolas P, Shai Y, 1994. Spectrum of antimicrobial activity and assembly of dermaseptin-b and its precursor form in phospholipid membranes. Biochemistry 33 : 10951–10960.
  31. Shai Y, 2002. Mode of action of membrane active antimicrobial peptides. Biopolymers 66 : 236–248.
  32. Mor A, Nicolas P, 1994. Isolation and structure of novel defensive peptides from frog skin. Eur J Biochem 219 : 145–154.
  33. Krugliak M, Feder R, Zolotarev VY, Gaidukov L, Dagan A, Ginsburg H, Mor A, 2000. Antimalarial activities of dermaseptin S4 derivatives. Antimicrob Agents Chemother 44 : 2442–2451.
  34. Dagan A, Efron L, Gaidukov L, Mor A, Ginsburg H, 2002. In vitro antiplasmodium effects of dermaseptin S4 derivatives. Antimicrob Agents Chemother 46 : 1059–1066.
  35. Ghosh JK, Shaool D, Guillaud P, Ciceron L, Mazier D, Kustanovich I, Shai Y, Mor A, 1997. Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis. J Biol Chem 272 : 31609–31616.
  36. Efron L, Dagan A, Gaidukov L, Ginsburg H, Mor A, 2002. Direct interaction of dermaseptin S4 aminoheptanoyl derivative with intraerythrocytic malaria parasite leading to increased specific antiparasitic activity in culture. J Biol Chem 277 : 24067–24072.

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  • Received : 12 Jan 2004
  • Accepted : 17 Mar 2004

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