RESUMEN

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. It 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.

Asunto(s)

Antiprotozoarios , Plasmodium falciparum/enzimología , Proteína Disulfuro Isomerasas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cromatografía de Afinidad , Cromatografía en Gel , Clonación Molecular , Colombia , Humanos , Datos de Secuencia Molecular , Peso Molecular , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Proteína Disulfuro Isomerasas/aislamiento & purificación , Proteína Disulfuro Isomerasas/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Tanzanía , Tailandia