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

G. Gregoriadis, A. Fernandes, M. Mital, B. McCormack

Research output: Contribution to journalReview articlepeer-review

80 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1964-1969
Number of pages6
JournalCellular and Molecular Life Sciences
Volume57
Issue number13-14
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Asparaginase
  • Catalase
  • Colominic acid
  • Polysialic acids

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