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Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics

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Abstract.

Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the body. Following intravenous injection, polysialic acids exhibit long half-lives in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysialic acids can be used as a means to increase the circulatory half-life of proteins and thus serve as an alternative to the nonbiodegradable monomethoxypoly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparaginase leads to a considerable increase of enzyme stability in the presence of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation significantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to prolong the circulation of peptides and proteins.

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Received 2 March 2000; accepted 15 June 2000

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Gregoriadis*, G., Fernandes**, A., Mital, M. et al. Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics. CMLS, Cell. Mol. Life Sci. 57, 1964–1969 (2000). https://doi.org/10.1007/PL00000676

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  • DOI: https://doi.org/10.1007/PL00000676

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