Receptor-based identification of an inhibitory peptide against blood stage malaria.
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.
Li
Xuerong
X
Department of Pharmacology and Cancer Center, University of Illinois College of Medicine, 909 South Wolcott Avenue, Room 5100, MC 704, Chicago, IL 60612, USA.
Chen
Huiqing
H
Khan
Anwar A
AA
Lauterbach
Sonja B
SB
Lanzillotti
Roberto
R
Rai
Prakash R
PR
Kane
Ravi S
RS
Coetzer
Theresa L
TL
Chishti
Athar H
AH
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology; D006021:Glycophorins / Q000737:chemistry; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology*; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D019151:Peptide Library; D010963:Plasmodium falciparum / Q000187:drug effects*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*
D000962:Antimalarials; D006021:Glycophorins; D009842:Oligopeptides; D019151:Peptide Library; D015800:Protozoan Proteins; C532881:glutamyl-threonyl-threonyl-leucyl-lysyl-seryl-phenylalanine
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