Cloning of Plasmodium falciparum protein disulfide isomerase homologue by affinity purification using the antiplasmodial inhibitor 1,4-bis{3-[N-(cyclohexyl methyl)amino]propyl}piperazine

A series of 10 1,4-bis(3-aminopropyl)piperazine compounds was found to display antiplasmodial activity with 50% growth inhibition between 30 and 250 nM, on three Plasmodium falciparum strains differently sensitive to chloroquine, By affinity chromatography using one of these compounds, a 52-kDa protein was isolated from P, falciparum, microsequenced and cloned, If corresponded to a single copy gene encoding a 453 amino acid protein displaying the typical features of protein disulfide isomerases, a thiol metabolizing enzyme belonging to the thiol: disulfide oxidoreductase superfamily, which was not previously described in malarial species. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.