Synthesis of Maleimide-End Functionalized Star Polymers and Multimeric Protein-Polymer Conjugates.
Synthesis of Maleimide-End Functionalized Star Polymers and Multimeric Protein-Polymer Conjugates.
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DOI：
10.1021/ma901540p
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发表时间：
2009-11-10
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：
Tao L;Kaddis CS;Loo RR;Grover GN;Loo JA;Maynard HD
蛋白质-聚合物缀合物表现出比未修饰的蛋白质优越的上级性质，在医学、生物技术和纳米技术领域对这些材料产生了很高的需求。预测多聚体缀合物超过单体缀合物的活性。在此，我们报告了一种简单的方法来合成多聚体聚合物缀合物。在四官能化三硫代碳酸酯链转移剂（CTA）存在下，通过可逆加成-断裂链转移（RAFT）聚合合成了四臂聚N-异丙基丙烯酰胺（pNIPAAm）。通过凝胶渗透色谱（GPC）、动态光散射凝胶渗透色谱（DLS-GPC）和基质辅助激光解吸/电离飞行时间（MALDI-TOF）质谱对聚合物的分子量、结构和多分散指数（PDI）进行了验证。该方法提供了明确定义的聚合物（PDI < 1.06）和针对各种分子量的能力。通过在呋喃保护的偶氮引发剂存在下加热聚合物，在链末端引入马来酰亚胺官能团。这允许V131 C T4溶菌酶与聚合物的位点特异性缀合以产生多聚体蛋白质-聚合物缀合物。MALDI-TOF质谱、电喷雾离子化气相色谱-迁移率大分子分析（ESI-GEMMA）、凝胶电泳和液相色谱-串联质谱（LC-MS/MS）证明了多聚体蛋白-聚合物结合物的形成。这种简单的策略提供了容易获得的星星蛋白质-聚合物缀合物，用于药物发现、药物递送和纳米技术领域。
Protein-polymer conjugates exhibit superior properties to unmodified proteins, generating a high demand for these materials in the fields of medicine, biotechnology, and nanotechnology. Multimeric conjugates are predicted to surpass the activity of monomeric conjugates. Herein, we report a straightforward method to synthesize multimeric polymer-conjugates. Four armed poly(N-isopropylacrylamide) (pNIPAAm) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of a tetra-functionalized trithiocarbonate chain transfer agent (CTA). The polymer molecular weight, architecture and polydispersity index (PDI) were verified by gel permeation chromatography (GPC), dynamic light scattering gel permeation chromatography (DLS-GPC), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. This approach afforded well-defined polymers (PDI's < 1.06) and the ability to target various molecular weights. Maleimide functional groups were introduced at the chain ends by heating the polymers in the presence of a furan-protected azo-initiator. This allowed for site-specific conjugation of V131C T4 lysozyme to the polymers to generate multimeric protein-polymer conjugates. MALDI-TOF mass spectrometry, electrospray ionization gas-phase electrophoretic-mobility macromolecule analysis (ESI-GEMMA), gel electrophoresis, and liquid chromatography tandem mass spectrometry (LC-MS/MS) of the trypsin digests demonstrated that multimeric protein-polymer conjugates had formed. This simple strategy provides ready access to star protein-polymer conjugates for application in the fields of drug discovery, drug delivery, and nanotechnology.
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影响因子：
15
作者：
Bontempo, D;Heredia, KL;Maynard, HD
通讯作者：
Maynard, HD
影响因子：
15
作者：
De, Priyadarsi;Li, Ming;Sumerlin, Brent S.
通讯作者：
Sumerlin, Brent S.
影响因子：
5.5
作者：
Boschmann, Daniel;Vana, Philipp
通讯作者：
Vana, Philipp
影响因子：
--
作者：
Boschmann, Daniel;Maenz, Martin;Vana, Philipp
通讯作者：
Vana, Philipp
影响因子：
15
作者：
Griffith, BR;Allen, BL;Kiessling, LL
通讯作者：
Kiessling, LL