Aims of the project
- Elucidation of the mechanism of action of heparanase
- Optimization of established heparanase inhibitors
- Design and synthesis of novel heparanase inhibitors, including glycomimetics
- Mapping binding sites of heparanase and identification of minimal heparanase binding sequences of heparan sulfate.
- Determination of structural requirements for recognition and inhibition of heparanase in sulfated polysaccharides of microbial, vegetal, and algal origin.
- Generation of sulfated polysaccharides highly active as heparanase-inhibitors, by regioselective sulfation/desulfation of selected polysaccharides, and of corresponding oligosaccharides of appropriate structure and size.
- Synthesis of oligosaccharides incorporating the minimal sequence binding to heparanase, as well of oligosaccharides and their mimetics recognized by heparanase but containing heparanase-resistant glycosidic bonds.
- Generation of novel potential anticancer drugs.