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

Cell Mol Life Sci. 2000 Dec;57(13-14):1964-9. doi: 10.1007/PL00000676.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Asparaginase / chemistry
  • Asparaginase / metabolism
  • Asparaginase / pharmacokinetics
  • Asparaginase / therapeutic use
  • Blood Proteins / pharmacology
  • Catalase / chemistry
  • Catalase / metabolism
  • Catalase / pharmacokinetics
  • Catalase / therapeutic use
  • Enzyme Stability / drug effects
  • Enzyme Therapy*
  • Enzymes / chemistry
  • Enzymes / metabolism
  • Enzymes / pharmacokinetics*
  • Half-Life
  • Humans
  • Kinetics
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism*

Substances

  • Blood Proteins
  • Enzymes
  • Sialic Acids
  • polysialic acid
  • Catalase
  • Asparaginase