Using synthetically modified proteins to make new materials.
Using synthetically modified proteins to make new materials.
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DOI：
10.1021/ar2001292
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发表时间：
2011-09-20
影响因子：
18.3
通讯作者：
Francis, Matthew B.
中科院分区：
文献类型：
--
作者：
Witus, Leah S.;Francis, Matthew B.
蛋白质独特多样的结构和功能为创造具有先进性能的新材料提供了许多令人兴奋的机会。利用这些能力需要一套多功能的化学反应，可以将非天然基团连接到蛋白质表面的特定位置。多年来，我们和其他人开发了一系列蛋白质生物缀合的新技术，特别强调实现高位点选择性和产量。利用这些反应，我们已经能够制备一些新材料，其功能取决于天然和合成成分。在本报告中，我们讨论了过去十年来我们在蛋白质生物缀合方面的进展，重点关注三个不同的项目。我们首先考虑我们的工作是通过模仿光合机构的特征来人工利用阳光，光合机构具有美丽的发色团，电子传递基团和催化中心的集成系统。这些光系统的中心是捕光天线，它有数百个精确排列的发色团，其位置由阵列内的蛋白质决定。我们的方法来产生类似的安排涉及烟草花叶病毒外壳蛋白的自组装轴承合成发色团。这些系统提供高效的光收集，易于制备，并可用于通过修饰蛋白质表面上的多个位点来构建复杂的光催化系统。然后，我们讨论蛋白质为基础的载体，可以提供药物和成像剂的病变组织。我们为此目的构建的纳米级代理是基于噬菌体MS 2的中空蛋白质外壳。这些27 nm的衣壳有32个孔，允许相对较大的有机分子进入蛋白质壳而不需要拆卸。我们的团队已经开发了一系列化学策略，可以在这些衣壳的内表面安装染料，放射性标记，MRI造影剂和抗癌药物。我们还开发了用癌细胞上特定蛋白质的粘合剂装饰外表面的方法。作为第三个研究领域，我们的团队开发了用于水修复的蛋白质-聚合物杂化材料。为了降低活细胞中重金属的毒性，自然界已经进化出金属硫蛋白，这是一种富含硫的多肽，可以结合汞，镉和其他有毒离子，浓度低于十亿分之一。不幸的是，这些蛋白质很难掺入聚合物中，主要是因为典型的蛋白质修饰反应靶向其正常功能所需的含有半胱氨酸、赖氨酸和羧酸盐的残基。为了应对这一挑战，我们开发了一种新的方法，通过将这些（和许多其他）蛋白质表达为N-和C-末端修饰“盒”的一部分，将它们连接到聚合物链上。由此产生的材料保持其选择性，并可以从海水中去除微量的有毒金属离子。这些实施例中的每一个都提出了一组新的蛋白质生物缀合挑战，这些挑战已经通过开发新的反应方法得到了满足。未来蛋白质基材料的生产将需要可扩展的合成技术，提高产量和选择性，廉价的生物缀合物纯化方法，以及通过蛋白质自组装设计新材料的理论和动力学处理。
The uniquely diverse structures and functions of proteins offer many exciting opportunities for creating new materials with advanced properties. Exploiting these capabilities requires a set of versatile chemical reactions that can attach nonnatural groups to specific locations on protein surfaces. Over the years, we and others have developed a series of new techniques for protein bioconjugation, with a particular emphasis on achieving high site selectivity and yield. Using these reactions, we have been able to prepare a number of new materials with functions that depend on both the natural and the synthetic components. In this Account, we discuss our progress in protein bioconjugation over the past decade, focusing on three distinct projects. We first consider our work to harness sunlight artificially by mimicking features of the photosynthetic apparatus, with its beautifully integrated system of chromophores, electron transfer groups, and catalytic centers. Central to these photosystems are light-harvesting antennae having hundreds of precisely aligned chromophores with positions that are dictated by the proteins within the arrays. Our approach to generating similar arrangements involves the self-assembly of tobacco mosaic virus coat proteins bearing synthetic chromophore groups. These systems offer efficient light collection, are easy to prepare, and can be used to build complex photocatalytic systems through the modification of multiple sites on the protein surfaces. We then discuss protein-based carriers that can deliver drugs and imaging agents to diseased tissues. The nanoscale agents we have built for this purpose are based on the hollow protein shell of bacteriophage MS2. These 27 nm capsids have 32 pores, which allow the entry of relatively large organic molecules into the protein shell without requiring disassembly. Our group has developed a series of chemical strategies that can install dyes, radiolabels, MRI contrast agents, and anti-cancer drugs on the inside surface of these capsids. We have also developed methods to decorate the external surfaces with binders for specific proteins on cancer cells. As a third research area, our group has developed protein–polymer hybrid materials for water remediation. To reduce the toxicity of heavy metals in living cells, Nature has evolved metallothioneins, which are sulfur-rich polypeptides that bind mercury, cadmium, and other toxic ions at sub-parts-per-billion concentrations. Unfortunately, these proteins are very difficult to incorporate into polymers, largely because typical protein modification reactions target the very cysteine, lysine, and carboxylate-containing residues that are required for their proper function. To address this challenge, we developed a new way to attach these (and many other) proteins to polymer chains by expressing them as part of an N- and C-terminal modification “cassette.” The resulting materials retain their selectivity and can remove trace amounts of toxic metal ions from ocean water. Each of these examples has presented a new set of protein bioconjugation challenges that have been met through the development of new reaction methodology. Future progress in the generation of protein-based materials will require scalable synthetic techniques with improved yields and selectivities, inexpensive purification methods for bioconjugates, and theoretical and dynamical treatments for designing new materials through protein self-assembly.
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