Synthesis of the O-linked pentasaccharide from Trypanosoma cruzi mucins containing the β-D-Galf-(1→2)-β-D-Galf motif

Abstract

Synthesis of the pentasaccharide β-D-Galf-(1→2)-β-D-Galf-(1→4)-[β-D-Galp-(1→3)-β-D-Galp-(1 → 6)]-D-GlcNAc found O-linked in mucins of epimastigote forms of Trypanosoma cruzi, the parasite responsible of Chagas disease (American trypanosomiasis) is described for the first time. The benzyl glycoside of the pentasaccharide efficiently inhibits parasite adhesion to the rectum of Chagas disease vector Triatoma infestans, a critical step leading to their differentiation into mammal-infective metacyclic forms. A [3+2] synthetic approach was followed, in which the thioglycosyde method of glycosylation was employed as key step. The pentasaccharide was also obtained by a sequential [3+1+1] strategy, however it was not as effective as the [3+2] approach due to migration of protecting groups.The benzyl glycoside showed to be acceptor of sialic acid catalyzed by T. cruzi trans-sialidase.