Trapping of Thiol Terminated Acrylate Polymers with Divinyl Sulfone to Generate Well-Defined Semi-Telechelic Michael Acceptor Polymers.
Trapping of Thiol Terminated Acrylate Polymers with Divinyl Sulfone to Generate Well-Defined Semi-Telechelic Michael Acceptor Polymers.
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DOI：
10.1021/ma901036x
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发表时间：
2009-10-27
期刊：
影响因子：
5.5
通讯作者：
Maynard HD
中科院分区：
文献类型：
--
作者：
Grover GN;Alconcel SN;Matsumoto NM;Maynard HD
本文报道了用可逆加成-断裂链转移（RAFT）聚合法合成乙烯基砜端功能化聚乙二醇化聚合物，用于偶联蛋白质。以2,2′-偶氮唑（2-甲基丙腈）为引发剂，在1-苯基乙基二硫苯甲酸酯存在下聚合聚乙二醇甲基醚丙烯酸酯（PEGA），通过凝胶渗透色谱（GPC）得到了数平均分子量（Mn）分别为6.7、11.8和16.1 kDa的聚乙二醇甲基醚丙烯酸酯（PEGA）。聚合后，大多数聚合物链在ω链端含有二硫酯官能团，聚合物的多分散性指数（PDI）在1.08 ~ 1.24之间。二硫酯随后通过氨解还原，得到的硫醇被二乙烯基砜原位捕获，得到半远旋乙烯基砜聚乙二醇，效率在85%到99%之间。测定了乙烯基砜的保留率与反应时间直接相关，30分钟内二硫酯转化为乙烯基砜的最大值。较长的反应时间导致乙烯砜端基分解缓慢。所得到的半远旋乙烯砜聚合物随后被偶联到含有游离半胱氨酸的蛋白质，牛血清白蛋白（BSA）。凝胶电泳表明，该反应是高效的，并且易于制备尺寸不断增大的缀合物。经聚合物附着后，BSA的活性为未修饰生物分子的92%。
Herein we report the synthesis of vinyl sulfone end functionalized PEGylated polymers by reversible addition-fragmentation chain transfer (RAFT) polymerization for conjugation to proteins. Poly(ethylene glycol) methyl ether acrylate (PEGA) was polymerized in the presence of 1-phenylethyl dithiobenzoate with 2,2′-azobis(2-methylpropionitrile) as the initiator to generate well-defined polyPEGAs with number-average molecular weights (Mn) by gel permeation chromatography (GPC) of 6.7 kDa, 11.8 kDa and 16.1 kDa. Post-polymerization, the majority of polymer chains contained the dithioester functional group at the omega chain end, and the polydispersity indexes (PDI) of the polymers ranged from 1.08 to 1.24. The dithioester was subsequently reduced via aminolysis, and the resulting thiol was trapped with a divinyl sulfone in situ to produce semi-telechelic, vinyl sulfone polyPEGAs with efficiencies ranging between 85% and 99%. It was determined that the retention of vinyl sulfone was directly related to reaction time, with the maximum dithioester being transformed into a vinyl sulfone within 30 minutes. Longer reaction times resulted in slow decomposition of the vinyl sulfone end group. The resulting semi-telechelic vinyl sulfone polymers were then conjugated to a protein containing a free cysteine, bovine serum albumin (BSA). Gel electrophoresis demonstrated that the reaction was highly efficient and that conjugates of increasing size were readily prepared. After polymer attachment, the activity of the BSA was 92% of the unmodified biomolecule.
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