Conjugation of 6-aminohexyl α-D-Galp-(1→3)-β-D-Galp with immunogenic peptides for the diagnosis of Chagas disease.

LOPEZ, ROSANA; GIORGI M. E; DE LEDERKREMER, ROSA M.; DUCREY, IVANA; CÁMARA, MARÍA DE LOS MILAGROS; BUSCAGLIA, CARLOS A.; MARINO, CARLA

Napoles

Congreso; Biennial Baltic Meeting on Microbial Carbohydrates 2020; 2022

Baltic Meeting on Microbial Carbohydrates

Trypanosoma cruzi is the etiological agent of Chagas disease, the most prevalent human parasitosis in Latin America, for which no vaccines or appropriate drugs are available. The routine diagnosis of this disease is based on the detection of antibodies against T. cruzi, using conventional serological techniques that present limitations in terms of their reproducibility, sensitivity and specificity. Therefore, the development of new tools or strategies for optimization of diagnosis of T. cruzi infection is of great interest. In our laboratory we develope and evaluate new diagnostic tools for Chagas disease, based on neoglycoconjugates containing, on one hand the epitope α-D-Galp-(1→3)-β-D-Galp (1), which is recognized by anti-α-galactosyl lytic antibodies present in sera of chronic chagasic patients,1 and on the other hand, antigenic peptides, whose structures are based on parasite mucin-associated surface proteins in mammal stages.2 The purpose is to improve the response of certain peptidic antigens, currently used as reagents for the serodiagnosis of Chagas disease, in mixed serological neoglycoproteins containing both epitopes, simultaneously.We synthesized disaccharide 1, derivatized with a spacer arm with an amino group (2), useful for conjugation. To obtain 2, precursors 4 and 5 were proposed. Acceptor 5 was prepared from tolyl β-D-1-thio-Galp through a sequence of reactions that did not require intermediate purifications. By glycosidation of 4 with 5, disaccharide 3 was stereoselectively obtained in good yield, which was later activated to introduce the 6-aminohexyl spacer arm.