Effects of Polymer Molecular Weight on the Size, Activity, and Stability of PEG-Functionalized Trypsin

被引：41

作者：

Chiu, Karen ^{[1
]}

Agoubi, Lauren L. ^{[1
]}

Lee, Iris ^{[1
]}

Limpar, Matthew T. ^{[1
]}

Lowe, James W., Jr. ^{[1
]}

Goh, Sarah L. ^{[1
]}

机构：

[1] Williams Coll, Dept Chem, Williamstown, MA 01267 USA

来源：

BIOMACROMOLECULES | 2010年 / 11卷 / 12期

关键词：

TRANSFER RAFT POLYMERIZATION; FREE-RADICAL POLYMERIZATION; ENZYME PRODRUG THERAPY; THERMAL-STABILITY; MACROMOLECULAR THERAPEUTICS; MODEL COMBINATION; IN-VIVO; PEGYLATION; PROTEIN; CHAIN;

D O I：

10.1021/bm1006954

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Polymer conjugation increases an enzyme's circulation time and stability for use as a therapeutic agent, but this attachment indubitably affects its properties. Covalent attachment of multiple polyethylene glycol chains with sizes of either 2, 5, 10, or 20 kDa increases the molecular weight and hydrodynamic radius of the model enzyme trypsin. The sizes of these polymer-enzyme conjugates are increased to be within the recommended limits for PDEPT applications. The T-d increases from 49 to 60 degrees C to expand the enzyme's workable range of conditions. This functionalization with PEG polymers of varying lengths maintains trypsin's enzymatic activity. Conjugate activities are 79-120% that of native trypsin at room temperature and 221-432% that of trypsin at 37 degrees C.

引用

页码：3688 / 3692

页数：5

共 38 条

[1]

Thiocarbonylthio compounds (S=C(Z)S-R) in free radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization). Effect of the activating group Z [J].