DISTRIBUTION OF MACROMOLECULAR METHYLATIONS IN PROMASTIGOTES OF LEISHMANIA-DONOVANI AND IMPACT OF SINEFUNGIN

Sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent both in vitro and in vivo. This mo lecule, structurally related to S-adenosylmethionine, is a good compet itive inhibitor of methyltransferases in vitro. The aim of this report is to analyze the impact of sinefungin on methylation pattern and the subcellular localisation of methyl groups and various methylases in p romastigotes of Leishmania donovani. We have shown the presence of var ious methylated macromolecules in different subcellular fractions, wit h somewhat higher concentration in membrane fraction. In vitro, sinefu ngin inhibits the three main protein methylases, but in cells cultured in its presence the protein carboxylmethylations are specifically inh ibited.