Synthesis of the hexasaccharide O-linked in Trypanosoma cruzi mucins, and selective sialylation by the trans-sialidase.

MENDOZA VM,; GIORGI M. E; AGUSTI R; GALLO- RODRIGUEZ C; LEDERKREMER RM

San Petesburgo

Congreso; ASMC 2007 International Symposium on Advances in Synthetic and Medicinal Chemistry.; 2007

ASMC

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 isinvolved in infection and pathogenesis.1 The O-chains in these mucin-like acceptors may be derivedfrom two cores, Galp(β1→4)GlcNAc or Galf(β1→4)GlcNAc, that are further branched with various unitsof Galf and/or Galp. The presence of Galf is related to the lineage of the T. cruzi strain. We haveundertaken the chemical synthesis of the Galf-containing oligosaccharides2 in order to correlatestructure with substrate activity in the TcTS reaction. We now report the synthesis ofGalp(β1→2)[Galp(β1→3)]Galp(β1→6)[ Galp(β1→2)Galf(β1→4)]GlcNAc as the benzyl glycoside 1 by 6-O-glycosylation of a convenient derivative of Galp(β1→2)Galf(β1→4)GlcNAc with a 2,3-di-O-(β-D-Galp)-D-Galp donor. The trichloroacetimidate method in acetonitrile as solvent, was used for selective βglycosylation.Hydrogenolysis of 1 and further reduction with NaBH4 gave alditol 2. NMR assignmentswere performed by analysis of mono and bidimentional spectra. Compounds 1 and 2 present threeterminal Galp for possible sialylation by TcTS. The acceptor properties were studied by usingrecombinant TcTS, sialyllactose as donor and analysis of reaction products by HPAEC-PAD. Conditionsfor selective sialylation will be presented.