Synthesis of Galp(alfa1-3) [Galp(beta1-6)]Galp, a model for studying the interplay between the anti--Galp antibody and the trans-sialylation in the infectivity of Trypanosoma cruzi

GIORGI, ME; MUCHNIK DE LEDERKREMER, R; MARINO, C

New Orleans

Simposio; XXVIII International Carbohydrate Symposium; 2016

International Carbohydrate Society

Trypanosomacruzi,theetiologic agent of Chagas disease, is covered by a dense glycocalix. In theepimastigote insect stage and in the trypomastigote infective stage, the mucinsare the main glycoprotein components of the glycocalix and are the acceptors ofsialic acid in a reaction catalyzed by trans-sialidase (TcTS).1Sialylationof trypomastigotemucins protects the parasite from lysis by the anti-aGal antibodiesin circulation. Acquisition of sialicacid from the host is essential for the infection, as the parasite is unable tobiosynthesize this sugar. TcTS specifically transfers asialic acidunit from aterminal b-Galp unit in the host glycoconjugate to terminal b-Galp unitsinthemucins to construct thea-NeuNAc-(2→3)-b-Galpmotif.On the other hand, although Galis the most abundant sugar in mucins of both trypomastigote and epimastigotestages,a-Galp isonly present in the first one whereas b-Galfis characteristicof the epimastigote stagein the less virulent strains. Whereas oligosaccharidesfrom epimastigotemucins are known,1 information on the finestructure of the carbohydrates in the trypomastigotemucins is still scarce.2We now report the synthesis of the titletrisaccharideas thep-thiotolylglycoside1, containing the antigenicunit a-Galpand a b-Galpthat may be acceptor of sialic acid. The synthetic strategy reliedon the synthesis of the conveniently protected disaccharide2with a free OH-6which could be selectiveyb-glycosylated with 3.Using acetylated trichloroacetimidate3a as donor,the protected derivative of1 was obtained and characterized byNMR spectroscopy. However,an undesirable by-product was formed byintermolecular migration of an acetyl group from 3a to disaccharide 2. Thereaction was improved using benzoylatedtrichloroacetimidate3b. Deprotectionby classical methods yieldedtrisaccharide1 which will be used for sialylationstudies with the TcTS and immunologic studies with the anti-a-Galp antibody.