Synthesis of the O-linked pentasaccharide in glycoproteins of Trypanosoma cruzi and selective sialylation by recombinant trans-sialidase.

MENDOZA, VM; AGUSTI, R; GALLO-RODRIGUEZ, C; MUCHNIK DE LEDERKREMER, R

CARBOHYDRATE RESEARCH

Elsevier

Lugar: Amsterdam; Año: 2006 vol. 341 p. 1488 - 1497

0008-6215

The mucin-like glycoproteins of Trypanosoma cruzi have a novel O-linked oligosaccharides which are acceptors of sialic acid in the trans-sialidase (TcTS) reaction. The transference of sialic acid from the host glycoconjugates to the mucins is involved in infection and pathogenesis. Synthesis of the pentasaccharide, b-D-Galp(1-2)[b-D-Galp(1-3)]-b-D-Galp(1-6)[b-D-Galf(1-4)]-D-GlcNAc and the corresponding alditol, previously isolated by reductive b-elimination of the mucins, is described. The key step was the 6-O-glycosylation of a convenient derivative of b-D-Galf(1-4)GlcNAc with a donor derivative of b-D-Galp(1-2)[b-D-Galp(1-3)]Galp by the trichloroacetimidate method. The b-linkage was diastereoselectively obtained by the nitrile effect. The pentasaccharide is the major oligosaccharide in the mucins of T. cruzi, G strain, and presents two terminal b-D-Galp for possible sialylation by TcTS. A preparative sialylation reaction was performed with its benzyl glycoside and the sialylated product was isolated and characterized. NMR spectroscopic analysis showed that selective mono-sialylation occurred at the terminal (1-3) linked galactopyranose.