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

被引：74

作者：

Gregoriadis, G ^{[1
]}

Fernandes, A ^{[1
]}

Mital, M ^{[1
]}

McCormack, B ^{[1
]}

机构：

[1] Univ London, Sch Pharm, Ctr Drug Delivery Res, London WC1N 1AX, England

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2000年 / 57卷 / 13-14期

关键词：

polysialic acids; colominic acid; catalase; asparaginase;

D O I：

10.1007/PL00000676

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1964 / 1969

页数：6