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聚(HPMA)-溶菌酶缀合物的合成与生物活性:新型噻唑烷-2-硫酮偶联化学的应用

Synthesis and bioactivity of poly(HPMA)-lysozyme conjugates: the use of novel thiazolidine-2-thione coupling chemistry.

作者信息

Tao Lei, Liu Jingquan, Xu Jiangtao, Davis Thomas P

机构信息

Centre for Advanced Macromolecular Design, School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.

出版信息

Org Biomol Chem. 2009 Sep 7;7(17):3481-5. doi: 10.1039/b907061c. Epub 2009 Jul 6.

DOI:10.1039/b907061c
PMID:19675903
Abstract

A novel thiazolidine-2-thione functionalized chain transfer agent (CTA) was synthesized and used as a reversible addition-fragmentation chain transfer (RAFT) polymerization agent to prepare well-defined poly-N-(2-hydroxypropyl) methacrylamide (PHPMA). The polymer chains had pre-designed molecular weights, narrow polydispersities and were chain-end functionalized. On incubation with protein (lysozyme) under different pH conditions, PHPMA was conjugated to the protein surface via covalent amide bonding. The bioactivity of the lysozyme-PHPMA conjugates was assessed using Micrococcus lysodeikticus (Ml) cells as substrates. The number of polymer chains attached to the protein could be controlled by both the pH of the conjugation reaction and the molecular weights of the polymers, thereby influencing significantly the bioactivity of the protein-polymer conjugates.

摘要

合成了一种新型的噻唑烷-2-硫酮官能化链转移剂(CTA),并将其用作可逆加成-断裂链转移(RAFT)聚合剂来制备结构明确的聚N-(2-羟丙基)甲基丙烯酰胺(PHPMA)。聚合物链具有预先设计的分子量,窄的多分散性并且链端官能化。在不同pH条件下与蛋白质(溶菌酶)孵育时,PHPMA通过共价酰胺键与蛋白质表面缀合。使用溶壁微球菌(Ml)细胞作为底物评估溶菌酶-PHPMA缀合物的生物活性。连接到蛋白质上的聚合物链的数量可以通过缀合反应的pH和聚合物的分子量来控制,从而显著影响蛋白质-聚合物缀合物的生物活性。

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