Mucins are highly O-glycosylated glycoproteins that are rich in serine and threonine repeating units, whose external oligosaccharides are linked to the protein via sugar units of a-N-acetyl-glucosamine (GlcNAc), in T. cruzi, or a-N-acetylgalactosamine (GalNAc), in mammals. In T. cruzi, these structures helps the parasite to interact with the infected host, while in vertebrates the functions of mucins range from being protective barriers to providing lubrication for epithelial cells. In tumor-related mucins, however, altered glycosylation is a common feature, being verified the presence of mono- and disaccharide structures known as TN and TF antigens,respectively. Therefore, this study describes the synthesis of the glycopeptides NHAc[�Gal]-(Thr)2-[aGalNAc]-(Thr)2-[aGlcNAc]-(Thr)2Gly-OVA 1  and NHAc[�Gal-aGalNAc]-(Thr)3-[aLacNAc]-(Thr)3-Gly-OVA 2   as mimetics of both T. cruzi and tumor mucins glycoproteins. These glycopeptides were obtained by solid phase synthesis, which involved the previous preparation of the protected glycosyl amino acids aGlcNAc-ThrOH 3  , aGalNAc-ThrOH 4  ,�Gal-ThrOH 5  ,aLacNAc-ThrOH 6   and �Gal-aGalNAc-ThrOH 7   by glycosylation reactions. Mice immunizations with glycopeptides 1   and 2  -OVA induced high antibodies titers (1/16000), as verified by ELISA tests, whereas flow cytometry assays showed the capacity of the obtained anti-glycopeptides 1   and 2   antibodies to recognize both T. cruzi and MCF-7 tumor cells. In addition, glycopeptides 1  and 2  antisera were also able to inhibit T. cruzi fibroblasts cells invasion (70%) and to induce an antibody-mediated cellular cytotoxicity (ADCC) against MCF-7 cells, with 50% reduction of cell viability. Taken together, these data point out glycopeptides 1  and 2  as potential dual synthetic vaccines against T. cruzi and breast tumor.

Synthetic glycopeptides mimicking both T. cruzi and tumor mucins show potential for vaccine development

248th National Meeting (2014)

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