title: Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics.
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.
authors.affiliation: Centre for Drug Delivery Research School of Pharmacy, University of London, United Kingdom. gregoriadis@cua.ulsop.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Gregoriadis
authors.forename: A
authors.initials: A
authors.lastname: Fernandes
authors.forename: M
authors.initials: M
authors.lastname: Mital
authors.forename: B
authors.initials: B
authors.lastname: McCormack
mesh_terms: D000818:Animals; D001215:Asparaginase / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001798:Blood Proteins / Q000494:pharmacology; D002374:Catalase / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D004795:Enzyme Stability / Q000187:drug effects; D057487:Enzyme Therapy; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D004798:Enzymes; D012794:Sialic Acids; C021319:polysialic acid; D002374:Catalase; D001215:Asparaginase