Plasmodium falciparum EBA-175 kDa protein peptides which bind to human redblood cells

Solid experimental evidence indicates that EBA-175 is used as a ligand by t he Plasmodium falciparum merozoite to bind to human RBC, via different bind ing processing fragments. Using synthetic peptides and specific receptor-li gand interaction methodology, we have identified 6 high-activity binding se quences from the EBA-175 CAMP strain; peptide 1758 (KSYGTPDNIDKNMSLIHKHN), located in the so-called region I for which no binding activity has been re ported before, peptides 1779 (NIDRIYDKNLLMIKEHILAI) and 1783 (HRNKKNDKLYRDE WWKVIKK), located in region II, in a sub-region known as 5' Cys F2, previou sly reported as being a binding region, and peptides 1814 (DRNSNTLHLKDPRNEE NERH), 1815 (YTNQNINISQERDLQKHGFH) and 1818 (NNNFNNIPSRYNLYDKKLDL), in regi on III-V where antibodies inhibit merozoite invasion of erythrocytes. The a ffinity constants were between 60 and 180 nM and the critical amino acids i nvolved in the binding were identified. The binding of these peptides to en zyme-treated RBC was analysed; binding of peptide 1814, located in the III- V region, was found to be sialic acid dependent. Some of these high binding peptides were able to inhibit in vitro merozoite invasion and to block the binding of recombinant RII-EBA ro RBC. Several of these peptides are locat ed in regions recognized by protective immune clusters of merozoites (ICMs) eluted antibodies.