Malaria invasion of human erythrocytes. Synthesis of peptides relevant to glycophorin A and evaluation of their inhibitory properties.
The objective of this study was to determine whether a nonglycosylated portion of glycophorin A (GPA), the main erythrocyte membrane glycoprotein, was involved in the process of invasion of red blood cells (RBC) by merozoites of Plasmodium falciparum, a parasite responsible for the most severe form of malaria. A series of peptides covering the sequence 55-76 situated upstream from the intramembraneous hydrophobic region of GPA was synthesized by an active ester coupling strategy and assessed for invasion-blocking capacity by using an in vitro assay system. Tests showed peptide 65-69, Ala-His-His-Phe-Ser, to be a good inhibitor of the invasion of RBC. Results presented here provide a confirmation of the existence of parasite binding sites on the peptide domain of GPA. Furthermore, comparison of inhibitory activity with peptide composition allowed us to rule out any contribution of a toxic parameter related to hydrophobicity as reported earlier.
Lacombe
J M
JM
Laboratory of Bioorganic Chemistry, University of Avignon, France.
Ferrari
B
B
Andriamananpisoa
R
R
Pavia
A A
AA
D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D006021:Glycophorins / Q000138:chemical synthesis* / Q000502:physiology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007202:Indicators and Reagents; D008288:Malaria / Q000097:blood*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*; D012795:Sialoglycoproteins / Q000138:chemical synthesis*
D006021:Glycophorins; D007042:Hypoxanthines; D007202:Indicators and Reagents; D009842:Oligopeptides; D012795:Sialoglycoproteins; D019271:Hypoxanthine