New method for the oxidation of saccharides
The enzyme heparanase acts at the cell suface or in the intercellular matrix to breakdown heparan sulphate (HS) molecules into oligosaccharides. Heparan sulphate is found in all animal tissues and regulates a number of biological activities. These include the growth of new blood vessels (angiogenesis), blood coagulation and tumour metastasis, when cancerous cells spread from one organ to another. Inhibiting the production of heparanase is considered to be a promising strategy for the development of new anti cancer drugs. This was achieved by the HEPARANASE project consortium by mapping binding sites of heparanase for HS and understanding how HS-like polysaccharides interact with enzymes, both as substrates and inhibitors. The heparanase inhibiting properties of polysaccharides were boosted by producing sulphation patterns optimised for antimetastatic-antiangiogenic activity. These targets were achieved by investigating the inhibition of heparanase with both natural and synthetic HS-like oligo/polysaccharides and its effect within living cells. A new method for the oxidation of the primary hydroxyl group of mono or oligosaccharides was developed by a HEPARANASE team from the University of Milan. It comprised two stages, the first being the oxidation to aldehyde with o-iodoxybenzoic acid (IBX). This was the first time that this method has been applied to carbohydrates. The second stage was to further oxidise to form the carboxyl group. This methodology enabled the efficient synthesis of hexuronic acid-containing disaccharides. The resulting compound had the framework of a glycosaminoglycan repeating unit.
