Receptor-based identification of an inhibitory peptide against blood stage malaria |
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Authors: | Li Xuerong Chen Huiqing Khan Anwar A Lauterbach Sonja B Lanzillotti Roberto Rai Prakash R Kane Ravi S Coetzer Theresa L Chishti Athar H |
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Institution: | a Department of Pharmacology and Cancer Center, University of Illinois College of Medicine, 909 South Wolcott Avenue, Room 5100, MC 704, Chicago, IL 60612, USA b Department of Molecular Medicine and Haematology, University of Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa c Department of Chemical & Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA |
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Abstract: | Plasmodium falciparum uses multiple host receptors to attach and invade human erythrocytes. Glycophorins have been implicated as receptors for parasite invasion in human erythrocytes. Here, we screened a phage display cDNA library of P. falciparum (FCR3, a sialic acid-dependent strain) using purified glycophorins and erythrocytes as bait. Several phage clones were identified that bound to immobilized glycophorins and contained the same 74 bp insert encoding the 7-amino acids sequence ETTLKSF. A similar screen using intact human erythrocytes in solution identified additional phage clones containing the same 7-amino acids sequence. Using ELISA and immunofluorescence, direct binding of ETTLKSF peptide to glycophorins and erythrocytes was confirmed. Pull-down and protease treatment assays suggest that ETTLKSF peptide specifically interacts with glycophorin C. The synthetic ETTLKSF peptide partially blocks merozoite invasion in human erythrocytes. Further characterization of ETTLKSF peptide could lead to the development of a novel class of inhibitors against the blood stage malaria. |
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Keywords: | Malaria Phage display Erythrocytes Plasmodium falciparum Glycophorin C EBA140 |
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