Development of α-D-Galp-(1→3)-β-D-Galp containing neoglycoconjugates for Chagas disease serodiagnosis

GIORGI, M. EUGENIA; CÁMARA, MARÍA DE LOS MILAGROS; MARINO, CARLA; LOPEZ, ROSANA; MELGAREJO, LINDA TORO; DE LEDERKREMER, ROSA M.; DUCREY, IVANA; BALOUZ VIRGINIA; BUSCAGLIA, CARLOS A.

Buenos Aires

Simposio; 3rd Argentinian Symposium on Glycobiology (GlycoAR2019); 2019

UNSAM

The immunodominant glycotope α-D-Galp-(1→3)-β-D-Galp-(1→4)-D-GlcNAc, expressed in the mucins of the infectivetrypomastigote stage of Trypanosoma cruzi has been proposedfor multiple clinical applications, from serodiagnosis of protozoancaused diseases to xenotransplantation or cancer vaccinology. Itwas previously shown that the analogue trisaccharide, with Glcin the reducing end instead of GlcNAc, was as efficient as thenatural trisaccharide for recognition of antibodies to α-D-Galp-(1→3)-β-D-Galp-(1→4)-D-GlcNAc elicited in T. cruzi-infectedindividuals. We describe here the synthesis of α-D-Galp-(1→3)-β-D-Galp-(1→4)-D-Glcp and α-D-Galp-(1→3)-β-D-Galp bothfunctionalized as the 6-aminohexyl glycoside and theirconjugation to BSA. For the synthesis of the trisaccharide alactose derivative, which already had the β-D-Galp-(1→4)-β-DGlcp motif, was used as starting material. For conjugation, thesquarate method was chosen, which allowed the directderivatization of the lysines amino groups of BSA by thecarbohydrate moieties. The synthesized neoglycoconjugateswere structurally characterized by SDS-Page and MALDI-TOFMS. Immunoassays indicated that they were specificallyrecognized by serum samples of T. cruzi-infected patients, andhence constitute suitable and much needed tools for theimprovement of Chagas disease diagnostic applications.