New detachable poly(ethylene glycol) conjugates: Cysteine-cleavable lipopolymers regenerating natural phospholipid, diacyl phosphatidylethanolamine

被引：152

作者：

Zalipsky, S ^{[1
]}

Qazen, M ^{[1
]}

Walker, JA ^{[1
]}

Mullah, N ^{[1
]}

Quinn, YP ^{[1
]}

Huang, SK ^{[1
]}

机构：

[1] Alza Corp, Menlo Park, CA 94025 USA

来源：

BIOCONJUGATE CHEMISTRY | 1999年 / 10卷 / 05期

关键词：

D O I：

10.1021/bc990031n

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

A new strategy for the reversible attachment of methoxypoly(ethylene glycol) (mPEG) to an amino-containing substrate is described. The strategy is based on formation of a benzyl carbamate linkage substituted with a disulfide in the para or ortho position. While being stable under nonreducing conditions, the dithiobenzyl (DTB) urethane linkage is susceptible to cleavage by mild thiolysis with cysteine resulting in release of the parent amino component of the conjugate in its original form. The method is exemplified by preparation of mPEG-DTB-alcohol, its activation and attachment to distearoylphosphatidylethanolamine (DSPE). The resulting lipopolymer incorporates into liposomes, which are capable of losing their polymer coating under conditions approximating those existing in vivo. Implications for drug delivery are briefly discussed.

引用

页码：703 / 707

页数：5

共 18 条

[1] A GENERAL STRATEGY FOR ELABORATION OF THE DITHIOCARBONYL FUNCTIONALITY, -(C=O)SS- - APPLICATION TO THE SYNTHESIS OF BIS(CHLOROCARBONYL)DISULFANE AND RELATED DERIVATIVES OF THIOCARBONIC ACIDS [J].