Thiosugars as building blocks for the synthesis of multivalent ligands

MARÍA LAURA UHRIG

Villa General Belgrano, Córdoba

Simposio; 2nd Argentinean Symposium of Glycobiology; 2016

Protein-carbohydrate interactions are involved in a variety of cellular recognition events. In natural systems, the weak binding affinity of carbohydrates for their protein receptors is overcome by the multivalent display of sugar residues at the surface of cells, which leads to the ?glycoside clustering effect?. A variety of multivalent ligands, compounds which expose several copies of a target sugar, were designed and synthesized, in the search of new mechanisms to interfere with these processes. Improved methodologies to obtain high-valency glycoclusters through high-yielding optimized processes are required. The most frequent approach involves the covalent bonding of several copies of a fragment containing the O-linked saccharide (previously obtained by classical glycosylation reactions) to multi-functionalized platforms using the copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction, also known as the ?click reaction?. Taking into consideration that O-glycosides are sensitive to glycosidases, we selected thioglycosides as building blocks for the construction of the ligands. Thiosugars are sugar mimetics in which the interglycosidic linkage was replaced by a sulfur atom. This replacement does not interfere with the recognition events and makes the sugar more resistant towards enzymatic and acidic hydrolysis. In this context, this presentation will focus on some of the synthetic strategies carried out in our group for the synthesis of multivalent ligands exposing glycomimetic structures and their affinity studies toward complementary lectins.