The isoprenoid-precursor dependence of Plasmodium spp

Natural Product Reports
Jan-Ytzen van der Meer, Anna K H Hirsch

Abstract

Due to the increase in resistance of Plasmodium spp. against available antimalarials, there is a need for new, effective and innovative drugs. The non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, which is absent in humans, is suggested as an attractive source of targets for such drugs with a novel mode of action. The biological importance of this pathway to Plasmodium spp. is proven by the efficacy of the clinical candidate fosmidomycin, which inhibits the biosynthesis of isoprenoid precursors; it is, however, less clear which isoprenoid end products are essential for parasite survival. In this Highlight, we identify protein prenylation, isoprene-containing quinone production, N-linked glycosylation as well as carotenoid and vitamin-E biosynthesis as probably essential isoprenoid-dependent physiological processes in Plasmodium. Inhibition of any of these processes blocks parasite development. Furthermore, both protein prenylation of SNARE proteins and a protein tyrosine phosphatase as well as tRNA prenylation have been identified as isoprene-dependent processes for which the physiological role in Plasmodium remains unclear. Therefore, the biosynthetic route to the isoprenoid precursors present...Continue Reading

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Citations

Jul 17, 2013·Drug Discovery Today·Tiziana MasiniAnna K H Hirsch
Apr 24, 2013·ACS Medicinal Chemistry Letters·Yonghui ZhangEric Old-Field

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