Suramin and Suramin Analogues Inhibit Merozoite Surface Protein-1 Secondary Processing and Erythrocyte Invasion by the Malaria Parasite Plasmodium falciparum

Abstract

Malarial merozoites invade erythrocytes; and as an essential step in this invasion process, the 42-kDa fragment of Plasmodium falciparum merozoite surface protein-1 (MSP142) is further cleaved to a 33-kDa N-terminal polypeptide (MSP133) and an 19-kDa C-terminal fragment (MSP1 19) in a secondary processing step. Suramin was shown to inhibit both merozoite invasion and MSP142 proteolytic cleavage. This polysulfonated naphthylurea bound directly to recombinant P. falciparum MSP142 (Kd = 0.2 μM) and to Plasmodium vivax MSP1 42 (Kd = 0.3 μM) as measured by fluorescence enhancement in the presence of the protein and by isothermal titration calorimetry. Suramin bound only slightly less tightly to t..