Inhibition of the enzyme heparanase overexpressed by tumors prevents not only the release and activation of angiogenic growth factors stored by heparan sulfate (HS) proteoglycans but also the disruption of the basement membrane and the extracellular matrix, and is regarded as a very promising approach to develop anticancer drugs
This project aims at:
- mapping the binding sites of heparanase for HS;
- determining the structural requirements of HS-like polysaccharides for interaction with the enzyme as substrates and as inhibitors;
- improving the heparanase-inhibiting properties of polysaccharides by generating specific sulfation patterns optimized on biological activity (inhibition of heparanase, antimetastatic-antiangiogenic activity).