title: Interaction of iron(II)-heme and artemisinin with a peptide mimic of Plasmodium falciparum HRP-II.
abstract: 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.
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex 4, France.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.forename: Sophie A-L
authors.initials: SA
authors.lastname: Laurent
authors.forename: Honoré
authors.initials: H
authors.lastname: Mazarguil
authors.forename: Michel
authors.initials: M
authors.lastname: Meyer
authors.forename: Anne
authors.initials: A
authors.lastname: Robert
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000737:chemistry* / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
chemical_list: D037621:Artemisinins; D010455:Peptides; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein; D006418:Heme; C031327:artemisinin; D007501:Iron