Interaction of iron(II)-heme and artemisinin with a peptide mimic of Plasmodium falciparum HRP-II.

The interaction of heme or heme-artemisinin adducts (heme-art) with different peptides mimicking repeat sequences of the Histidine-Rich-Protein-II of Plasmodium falciparum (PfHRP-II) was investigated. The pseudo-first order rate constants of the coordination of heme or heme-art onto a histidine rich peptide, used as a mimic of PfHRP-II putative heme binding sequence, are of the same order of magnitude, namely 42 and 14 s(-1), respectively. Despite the intrinsic reactivity of the carbonyl at C10 of heme-art toward a hydroxyl function, a peptide containing a serine or threonine residue does not readily react with heme-art adducts. Therefore, a much higher affinity of heme-art compared to heme toward PfHRP-II, if so, must be induced by a specific interaction or a chemical reaction, these phenomena being both due to the tertiary structure of the parasite protein itself.