The surface of the protozoan parasite Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, is heavily coated by glycoproteins containing highly immunogenic O-glycans. My research group has previously synthesized eleven T. cruzi related saccharides with either non-reducing terminal a-galactosyl or a-rhamnosyl moieties related to these O-glycans and conjugated them to bovine serum albumin (BSA) for the generation of a glycoarray in a microplate format. The recognition of the saccharides by antibodies was studied by chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) using pooled sera from patients with chronic Chagas disease. The study revealed the disaccharide Gala(1,3)Gal� as the immunodominant glycotope, however, the study had not included the disaccharide Gala(1,3)Gala, and therefore the role played by the anomeric configuration of the reducing end sugar is not known. Here we present the synthesis of the disaccharide Gala(1,3)Gala and its conjugation to BSA for CL-ELISA studies. This disaccharide has been synthesized using known protecting group strategies, and was fully characterized using NMR spectroscopy and mass spectrometry. The disaccharide was then covalently linked to an Fmoc-protected amino acid for incorporation into a peptide, which will later be studied as a potential B-cell and T-cell epitope.  This work has implications for the development of a fully synthetic carbohydrate-based vaccine, and diagnostic and chemotherapy follow-up biomarkers for Chagas disease.

Synthesis of the disaccharide aGal-1,3-aGal and its conjugation to a carrier protein

247th National Meeting (2014)

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