Synthesis of Galp(α1→3) [Galp(β1→6)]Galp, a model for studying the interplay between the anti α-Galp antibody and the trans-sialylation in the infectivity of Trypanosoma cruzi

MARINO, CARLA; GIORGI M. E; LEDERKREMER R. M.

New Orleans, Louisiana

Simposio; XXVIII International Carbohydrate Symposium I.C.S 2016; 2016

International Carbohydrate Organization

Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix. In the epimastigote insect stage and in the trypomastigote infective stage, the mucins are the main glycoprotein components of the glycocalix and are the acceptors of sialic acid in a reaction catalyzed by trans-sialidase (TcTS).1 Sialylation of trypomastigote mucins protects the parasite from lysis by the anti-α-Galp antibodies in circulation. Acquisition of sialic acid from the host is essential for the infection, as the parasite is unable to biosynthesize this sugar. TcTS specifically transfers a sialic acid unit from a terminal β-Galp unit in the host glycoconjugate to terminal β-Galp units in the mucins to construct the α-NeuNAc-(2→3)-β-Galp motif. On the other hand, although Gal is the most abundant sugar in mucins of both trypomastigote and epimastigote stages, α-Galp is only present in the first one whereas β-Galf is characteristic of the epimastigote stage in the less virulent strains. Whereas oligosaccharides from epimastigote mucins are known, information on the fine structure of the carbohydrates in the trypomastigote mucins is still scarce.2 We now report the synthesis of the title trisaccharide as the p-thiotolyl glycoside 1, containing the antigenic unit α-Galp and a β-Galp that may be acceptor of sialic acid. The synthetic strategy relied on the synthesis of the conveniently protected disaccharide 2 with a free OH-6 which could be selectivey β-glycosylated with 3. Using acetylated trichloroacetimidate 3a as donor, the protected derivative of 1 was obtained and characterized by NMR spectroscopy. However, an undesirable by-product was formed by intermolecular migration of an acetyl group from 3a to disaccharide 2. The reaction was improved using benzoylated trichloroacetimidate 3b. Deprotection by classical methods yielded trisaccharide 1 which will be used for sialylation studies with the TcTS and immunologic studies with the anti-α-Galp antibody.