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.