SYNTHESIS AND AFFINITY FOR MANNOSE BINDING LECTIN OF MULTIVALENT SACCHARIDE COMPOUNDS

Stroke is the third cause of death and the first cause of long-term disability in developed countries. An ischemic attack induces a complex series of acute and delayed cellular and molecular events. After the acute phase, the lesion does indeed continue growing for many hours and even days. When blood flow restarts in a tissue hit by an ischemic injury, reperfusion leads to the extent of injury. Inflammation takes place and the activation of complement system can amplify tissue damage. On the other hand, endogenous inhibitors of complement, in particular the inhibition of lectin pathway, is a very promising therapeutic strategy¹. MBL is a trimeric C-type lectin, containing three carbohydrate recognition domains which bind to oligosaccharides containing D-mannose and N-acetyl D-glucosamine. Inhibition of MBL by using carbohydrate multivalent structures is the general aim of this project². We focused our attention to oligosaccharides composed by β(1→4)-linked N-Acetyl glucosamine residues. In this communication we will describe the synthesis of monomer, dimer and linear trimer. Our synthetic strategy is based on a sequence of glycosylations with trichloroacetimidate and thioglycoside as glycosyl donors. The reducing terminus of each target compound is endowed with an azidoethyl linker in anomeric position. This linker allowed the conjugate of these ligands to a tetravalent dendrimer via CuAAC to enable multivalent interaction.