Polysialylated proteins - An approach to improving enzyme stability and half-life in the blood circulation

Naturally occurring polymers of N-acetyl neuranimic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the b ody. Following intravenous injection, polysialic acids exhibit long half li ves in the blood circulation and have therefore been proposed as carriers o f short-lived drugs and small peptides. In addition, shorter-chain polysial ic acids can be used as a means to increase the circulatory half-life of pr oteins and thus serve as nit alternative to the non-biodegradable monometho xy poly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and aspa raginase leads to a considerable increase of enzyme stability in the presen ce of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation signi ficantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to pr olong the circulation of peptides and proteins.