Synthesis of the O-linked pentasaccharide containig β-D-Galf-(1→2)-β-D-Galf in Trypanosoma cruzi mucins

GUSTAVO A. KASHIWAGI; ROSA M. DE LEDERKREMER; CARMEN R. CORI CALIZAYA; CAROLA GALLO-RODRIGUEZ

Washington

Congreso; 254th ACS National Meeting; 2017

American Chemical Society

The protozoan Trypanosoma cruzi es the ethiologic anget of Chagas disease, the American trypanosomiasis wich is transmitted to animals and humans by insect vectors of the family Reduviidae. A dense glycocalix covers the surface of the parasite and its composition is characteristic of each differentiation stage of the complex living cycle.The mucin-like glycoproteins are major components in the protozoan surface. The oligosaccharides in the mucins are O-linked to the protein (threonine) by a a-GlcNAc instead of GalNac common in vertebrate mucins. They are derived from two cores, Galp(b1-4)GlcNAc or Galf(b1-4)GlcNAc. The cores are further branched by Galf or Galp. The terminal b-D-Galp residues are acceptors of sialic acids in the trans-sialidease reaction, wich is involved in the invasion of the host cells. Sialic acid is not biosynthesized by the parasite. The presence of b-Galf is related to the lineage of the T. cruzi strain and it is restricted to the epimastigote stage. The biosynthetic studies for the incorporation of Galf are important since this unit is not biosynthesized by mammals. In our laboratory, we have undertaken the chemical synthesis of the Galf constaining oligosaccharides, with the aim to corralate their strutcture with the ability to act as substrates, in the reaciton of trsans sialidation.The pentasaccharide b-D-Galf(1-3)b-D-Galp(1-6)-[b-d-Galf(1-2)b-D-Galf(1-4)]D-GlcNAc-ol was isolted from the Tulahuen strain by b-elimination. This structure is part of the hexasaccharide slditol obtained from mucins of the Tulahuen strain, wich was recently synthetized by our group. We know report the synthetic studies towards the pentasaccharide b-D-(1-3)b-D-Galp(1-6)[b-D-Galf(1-2)b-D-Galf(1-4)]D-GlcNAc as a-benzyl glycoside 1. A [3+2] convergent approach was followed using trisaccharide 2 with an internal Galf as acceptor. The differences on the glycosylation method using thiglycoside 3 and trichloroacetimidate 4 as donors for the construction of the b-D-Galp (1-6) -D-GlcNAc linkage will be discuted.