Neoglycoconjugates of antigenic oligosaccharides. Synthesis of Galp(a1→3)Galp(b1→4)GlcNAc--L-Threo

POKLEPOVICH CARIDE, S.; AGUSTI, R; MUCHNIK DE LEDERKREMER, R; MARINO, C

Buenos Aires

Simposio; First Argentinian Symposium of Glycobiology; 2014

(1428), Argentina. E-mail: cmarino@qo.fcen.uba.ar The O-linked chains of Trypanosoma cruzi mucins present some particular features. For example, the presence of a-Galp in trypomastigotes and b-Galf in epimastigotes and metacyclic is unique and both configurations are highly immunogenic. On the other hand, contrary to the protein, the sugar structures have a characteristic pattern that depends not only of the stage but also of the strain. The presence of antibodies against saccharidic epitopes plays a relevant role in the infection process. Synthetic oligosaccharides and their conjugates are currently used for the diagnostic of several diseases. We describe here preliminary studies on the synthesis of Galp(α1-3)Galp(β1-4)GlcNAc-a-threo (1), containing the minimum antigenic oligosaccharidic structure found in trypomastigote mucins detected by sera from chronic chagasic patients. With the aim of establishing a high-yielding procedure for such synthesis and thus produce glycoconjugate 1 with the efficiency and low cost required for its clinic use, we proposed the use of 2,3,4,6-tetra-O-benzyl-b-d-Galp trichloroacetimidate, (2), tolyl 4-O-acetyl-2-benzoyl-6-O-tertbutyldiphenylsilyl-b-d-1-thio-Galp (4) and 6-O-tertbutyldiphenylsilyl-2-acetamido-2-deoxy-b-d-Glcp-l-Threo (5) as building blocks. Studies on the regioselectivity of the glycosylation of 5 and spectroscopical characterization of synthetic intermediates will be present.