Study of the interaction of thiogalactoside analogues with Peanut agglutinin and human Galectin-3

KOVENSKY, JOSÉ; CAGNONI, ALEJANDRO JAVIER; MARÍA LAURA UHRIG

Bangalore

Congreso; International Carbohydrate Symposium; 2014

Internationa Carbohydrate Society

We report the rational design and synthesis of a new family of multivalent ligands bearing thiodigalactoside (TDG) analogues as recognition elements (RE). These ligands proved to be resistant to the enzymatic activity of E. coli β-galactosidase, therefore a better bioavailability and a higher life-time in vivo may be expected, compared to O-glycosides. Taking into account previous reports,1 their affinity to β-galactoside-binding lectins, peanut agglutinin (PNA) and human galectin-3 (hGal-3), was determined by isothermal titration calorimetry. The glycoclusters exhibited a higher binding affinity with hGal-3 than with PNA, and a moderate multivalent effect was observed. In both cases, a monovalent ligand exhibited a higher binding affinity than the RE and TDG, suggesting a positive effect of the triazole ring in the biological activity. Docking studies were realized in order to evaluate specific interactions between the different HO- and hydrophobic groups, and key aminoacid residues in the carbohydrate recognition domain of both lectins. Additional interactions between the triazole ring and certain aminoacid residues of the lectins were observed. These interactions could account for the higher binding affinity of the monovalent ligands compared to the references.