The protozoan Trypanosoma cruzi is the ethiologic agent of Chagas disease, the American trypanosomiasis, which 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 α-GlcNAc instead of GalNAc common in vertebrate mucins. They are derived from two cores, Galp(β1→4)-GlcNAc or Galf(β1→4)-GlcNAc. The cores are further branched by Galf or Galp. The terminal β-Galp residues are acceptors of sialic acid in the trans-sialidase reaction, which is involved in the invasion of the host cells. Sialic acid is not biosynthesized by the parasite. The presence of β-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-containing oligosaccharides, with the aim to correlate their structure with the ability to act as substrates in the reaction of trans-sialidation. The pentasaccharide β-D-Galp(1→3)-β-D-Galp(1→6)-[β-D-Galf(1→2)-β-D-Galf(1→4)]-D-GlcNAc-ol, was isolated from the Tulahuen strain by reductive β-elimination. This structure is part of the hexasaccharide alditol obtained from mucins of the Tulahuen strain, which was recently synthetized by our group. We now report the synthetic studies towards the pentasaccharide β-D-Galp(1→3)-β-D-Galp(1→6)-[β-D-Galf(1→2)-β-D-Galf(1→4)]-D-GlcNAc as α-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 thioglycoside 3 and trichoroacetimidate 4 as donors for the construction of the β-D-Galp-(1→6)-D-GlcNAc linkage will be discussed.

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

254th National Meeting (2017)

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