Synthesis of the hexasaccharide, o-linked in trypanosoma cruzi mucins, and selective sialylation by the trans-sialidase

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

San Petesburgo, Rusia

Simposio; International Symposium on Advances in Synthetic and Medicinal Chemistry; 2007

Trypanosoma cruzi, the agent of American trypanosomiasis, expresses an unusual 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 acceptors may be derived from two cores, Galp(b1-4)GlcNAc or Galf(b1-4)GlcNAc, that 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. We have undertaken the chemical synthesis of the Galf-containing oligosaccharides2 in order to correlate structure with substrate activity in the TcTS reaction. We now report the synthesis of Galp(b1-2)[Galp(b1-3)]Galp(b1-6)[ Galp(b1-2)Galf(b1-4)]GlcNAc as the benzyl glycoside 1 by 6-O-glycosylation of a convenient derivative of Galp(b1-2)Galf(b1-4)GlcNAc with a 2,3-di-O-(b-D-Galp)-D-Galp donor. The trichloroacetimidate method in acetonitrile as solvent, was used for selective b-glycosylation. Hydrogenolysis of 1 and further reduction with NaBH4 gave alditol 2. NMR assignments were performed by analysis of mono and bidimentional spectra. Compounds 1 and 2 present three terminal Galp for possible sialylation by TcTS. The acceptor properties were studied by using recombinant TcTS, sialyllactose as donor and analysis of reaction products by HPAEC-PAD. Conditions for selective sialylation will be presented.