Heparan sulfates (HS) are linear polysulfated polysaccharides composed of alternate 1,4-linked uronic acid (either β-D-glucuronic acid (GlcUA) or α-L-iduronic acid (IdoA)) and α-D-glucosamine (GlcN). HS are widespread on the cell surfaces and in the extracellular matrix, capable of mediating and/or modulating various physiological processes, including blood coagulation, tissue repair and remodeling, development, angiogenesis, and bacterial and viral infections.
Interferon-γ(IFN-γ) is a cytokine that plays a vital role in the immune response and inflammatory processes. IFN-γis composed of a C2-symmetric homodimer that binds to HS by virtue of its basic residues located at the C terminus of the two subunits. We have shown that symmetric “head to head” HS mimetics, exhibiting also a C2-symmetry (Figure 1a) are nanomolar inhibitors of IFNγpro-inflammatory activity by preventing cytokine bonding both on HS and its receptor. After validating the feasibility of reducing-end (RE) and non-reducing end (NRE) modifications by click chemistry on a disaccharide model, we will present the strategy allowing preparation of HS long fragments mimetics with “tail to tail” and “head to tail” topologies (Figure 1b and 1c).
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