THE PLASMODIUM-FALCIPARUM TRANSLATIONALLY CONTROLLED TUMOR PROTEIN HOMOLOG AND ITS REACTION WITH THE ANTIMALARIAL DRUG ARTEMISININ

Artemisinin and its derivatives are important new antimalarial drugs. When Plasmodium falciparum-infected erythrocytes are incubated with [1 0-H-3]dihydroartemisinin, several malaria-specific proteins become lab eled. One of these proteins is the P. falciparum translationally contr olled tumor protein (TCTP) homolog. In vitro, dihydroartemisinin react s covalently with recombinant TCTP in the presence of hemin. The assoc iation between drug and protein increases with increasing drug concent ration, plateauing at approximately 1 drug/TCTP molecule. By Scatchard analysis, there appear to be 2 hemin binding sites on TCTP with disso ciation constants of similar to 18 mu M, When the single cysteine moie ty is blocked by pretreatment with iodoacetamide, hemin binding is not affected, whereas drug binding is reduced by two-thirds. Thus, TCTP r eacts with artemisinin in situ and in vitro in the presence of hemin a nd appears to bind to hemin, The function of the malarial TCTP and the role of this reaction in the mechanism of action of artemisinin await elucidation.