Protein-cross-linked polymeric materials through site-selective bioconjugation
Protein-cross-linked polymeric materials through site-selective bioconjugation
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DOI：
10.1002/anie.200705564
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Francis, Matthew B.
中科院分区：
文献类型：
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作者：
Esser-Kahn, Aaron P.;Francis, Matthew B.
由蛋白质和聚合物构建的定义良好的杂化材料为传感器、致动器和药物输送系统的构建提供了重要的机会。这些材料背后的使能概念是蛋白质的特定生物功能与合成聚合物的体积特性和可加工性的融合。最近的报告利用这一概念来生产基于若干不同投入而经历动态变化的材料。例子包括对离子、[1]肽、[2]抗原-[3]和碳水化合物结合相互作用、[4]细胞表面受体、[5]和温度的响应变化在一个特别明确的例子中，Murphy等人展示了聚合物与两个特定蛋白质位点的共价附着，有效地产生了生物分子交联。配体诱导的蛋白质构象变化使其体积发生了显著变化虽然这些开创性的研究带来了巨大的机会，但它们依赖于偶联技术，很难推广到所有的蛋白质和聚合物。位点选择性生物偶联是这类材料的核心，利用现代方法进行蛋白质活化[7-10]将为更广泛的材料提供途径。特别是，在两个位点上附着可能是有利的，这需要在两个位置选择性地修饰蛋白质的挑战。理想情况下，获取这些杂交种的方法将不依赖于初级序列，并将适用于广泛的蛋白质阵列。因此，我们以蛋白质末端为目标，因为它们提供了两种位点特异性的、化学上不同的修饰，它们独立于任何一种蛋白质，但对所有蛋白质都是通用的。这种附着策略也代表了一种将蛋白质的折叠状态与聚合物主链的性质联系起来的最佳方式。在此，我们报告了一种利用蛋白质构建蛋白质-聚合物杂化材料的方法
Well-defined hybrid materials constructed from proteins and polymers offer significant opportunities for the construction of sensors, actuators, and drug-delivery systems. The enabling concept underlying these materials is the fusion of the specific biological function of proteins with the bulk properties and processability of synthetic polymers. Recent reports have capitalized on this concept to produce materials that undergo a dynamic change based on a number of different inputs. Examples include changes in response to ions,[1] peptides,[2] antigen-[3] and carbohydrate-binding interactions,[4] cell surface receptors,[5] and temperature.[6] In a particularly welldefined example, Murphy et al. demonstrated the covalent attachment of polymers to two specific protein sites, effectively generating a biomolecular cross-link. Ligand-induced conformational changes in the protein then afforded a significant change in volume.[2] While these pioneering studies promise great opportunities, they have relied on coupling techniques that are difficult to generalize to all proteins and polymers. Site-selective bioconjugation is at the heart of such materials, and utilizing modern methods for protein activation [7–10] should provide access to a wider range of materials. In particular, it could be advantageous to attach at two sites, which requires the challenge of modifying proteins selectively at two locations. Ideally, the method for accessing these hybrids would not rely on the primary sequence and would be applicable to a wide array of proteins.We therefore targeted the protein termini because they provide two site-specific, chemically distinct modifications that are independent of any one protein and yet common to all. This attachment strategy also represents an optimal way to relate the folded state of the protein to the properties of the polymer backbone. Herein, we report a method for the construction of protein–polymer hybrid materials utilizing