Mechanisms of depolymerization and activation of a polysialic acid and its tetramer by hydrogen peroxide

Naturally occurring polysialic acid (PSA), appropriately functionalized, has been widely used in different biological products. The present paper describes an original approach which enables to both activate and depolymerize the PSA, by reacting with hydrogen peroxide. In order to understand the mechanisms, we investigate the course of H2O2 reactions with the native PSA and with a simpler model, the tetrasialic acid (4SA). Three recurrent reactions were observed. First, we detected a very fast and irreversible decarbonylation at the reducing end of the polysaccharide. Then, the hydroxyl radicals (generated via the Fenton reaction) were responsible for the depolymerization of glycosidic linkages by substitution reactions. Finally, the oxidation of hydroxyl groups led to the formation of carbonyl groups and the carbohydrate's activation.