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

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

Dubrovnik, Croatia

Congreso; Satellite Meeting to the 30th FEBS Congress and 9th IUBMB Conference. GLYCOPROTEOMICS: Protein modifications for versatile functions; 2005

  Trypanosoma cruzi, the agent of American trypanosomiasis, expresses an unusual surface trans-sialidase (TcTS) that transfers sialic acid from the host glycoconjugates to parasite glycoproteins. This process is involved in infection and pathogenesis.1 The O-chains, in these mucin-like sialic acid acceptors, are linked to the protein by a-GlcNAc and may be derived from two cores, Galp(b1?¨4)GlcNAc or Galf(b?¨4)GlcNAc. The cores are further branched with various units of Galf and/or Galp. The presence of Galf is related to the lineage of the T. cruzi strain (Fig. 1). In our laboratory we have undertaken the chemical synthesis2 of the Galf-containing oligosaccharides in order to correlate their structure with the ability to act as substrates in the reaction. We now report the synthesis of Galp(b1?¨2)[Galp(b1?¨3)]Galp(b1?¨6)[Galf(b1?¨4)]GlcNAc (1) by 6-O-glycosylation of a convenient derivative of Galf(b1?¨4)GlcNAc2 with a donor derivative of Galp(b1?¨2)[Galp(b1?¨3)]Galp.3 Pentasaccharide 1 is the major oligosaccharide in the mucins of T. cruzi strain G and presents two terminal b-D-Galp for possible sialylation in the trans-sialidase reaction. The acceptor substrate selectivity was studied for compound 1, its benzyl glycoside 2 and the corresponding alditol 3. A preparative reaction was performed with the benzyl glycoside 2 and the sialylated product was separated by anion exchange column chromatography and was analyzed by 1D- and 2D-NMR spectroscopy.