Biosynthesis of Galactofuranose in Kinetoplastids: Novel Therapeutic Targets for Treating Leishmaniasis and Chagas' Disease

Abstract

Cell surface proteins of parasites play a role in pathogenesis by modulating mammalian cell recognition and cell adhesion during infection.β-Galactofuranose (Galf) is an important component of glycoproteins and glycolipids found on the cell surface ofLeishmaniaspp. andTrypanosoma cruzi.β-Galf-containing glycans have been shown to be important in parasite-cell interaction and protection against oxidative stress. Here, we discuss the role ofβ-Galfin pathogenesis and recent studies on the Galf-biosynthetic enzymes: UDP-galactose 4′epimerase (GalE), UDP-galactopyranose mutase (UGM), and UDP-galactofuranosyl transferase (GalfT). The central role in Galfformation, its unique chemical mechanism, and the absence of a homologous enzyme in humans identify UGM as the most attractive drug target in theβ-Galf-biosynthetic pathway in protozoan parasites.