CAREER: Synthetically Modified Tobacco Mosaic Virus: A Versatile Scaffold for Nanoscale Materials

在化学系有机动力学项目的支持下，加州大学伯克利分校的马修·弗朗西斯教授将研究烟草花叶病毒(TMV)的管状衣壳，这为构建纳米材料提供了一个非常有希望的模板。每个粒子的长度为300纳米，由2100个相同的蛋白质亚基组成，这些蛋白质亚基可以将光学和电子元件定向成线状组装。然而，新功能的共价连接到衣壳上一直很难实现，部分原因是生物结合反应通常针对的氨基酸侧链在组装后没有在表面找到。为了应对这一挑战，弗朗西斯教授开发了化学正交合成方法，可以将小分子安装在衣壳外表面、中空核心衬里的表面或衣壳螺旋的两端。综上所述，这些修饰反应使TMV成为可用于构建纳米材料的最通用的构建块之一。利用生物分子构建纳米材料代表了器件制造的重大范式转变，因此出现了许多新的挑战。特别是，将聚合物、无机材料和其他功能组件结合到组件中一直很难实现。这些研究的一个关键组成部分是蛋白质组件在有机溶剂中的增溶作用，以应对这些挑战。这代表了许多蛋白质修饰的新途径，是一种非常有前途的稳定蛋白质二级结构和三级结构的方法。这也是制备基于蛋白质的Langmuir-Blodgett膜的一个重大进展，这种膜通常被与大多数蛋白质相关的水溶性所阻止。当与AFM和其他表面表征技术相结合时，这些新工具还将提供一个通用的实验平台，用于研究生物分子聚集。有机和高分子化学计划支持加州大学伯克利分校的Matthew Francis教授，他的研究预计将产生对生物分子用于材料合成的基本见解，特别强调基于蛋白质的结构将补充DNA可以用于的应用。拟议的研究计划最大的影响是它将为研究生和本科生提供独特的培训环境。所有学生将结合有机合成、物理有机化学和过渡金属化学以及与蛋白质相关的表达、纯化和表征方法。学生将拥有一套不同的技术技能，并将能够解决化学和生物交界处的跨学科问题。弗朗西斯教授将试图通过一项特别的努力来影响社区，让非科学家了解纳米技术。他将在扶轮社和其他地方组织举办一系列精力充沛的讲座，目的是描述纳米技术的深刻益处。类似的讲座将在当地社区的高中举行。

With the support of the Organic Dynamics Program in the Chemistry Division, Professor Matthew Francis of the University of California- Berkeley will work with the tube-like capsid of the tobacco mosaic virus (TMV), which provides an extremely promising template for the construction of nanoscale materials. Each particle is 300 nm in length and is made of 2100 identical protein subunits that could orient optical and electronic components into wire-like assemblies. However, the covalent attachment of new functionality to the capsid has been difficult to achieve, in part because the amino acid side chains commonly targeted by bioconjugation reactions are not found on the surface after assembly. To address this challenge, Professor Francis has developed chemically orthogonal synthetic methods that can install small molecules on the exterior capsid surface, the surface lining the hollow core, or at either end of the capsid helix. Taken together, these modification reactions render TMV one of the most versatile building blocks available for the construction of nanoscale materials. The use of biomolecules for the construction of nanoscale materials represents a major paradigm shift in device fabrication, and as a result many new challenges have emerged. In particular, the incorporation of polymers, inorganic materials, and other functional components into the assemblies has been difficult to achieve. A key component of these studies is the solubilization of protein assemblies in organic solvents to address these challenges. This represents many new avenues for protein modification and is a highly promising way to stabilize protein secondary and tertiary structure. It is also a significant advancement in the preparation of protein-based Langmuir-Blodgett films, which are often prohibited by the water solubility associated with most proteins. When combined with AFM and other surface characterization techniques, these new tools will also provide a versatile experimental platform with which to study biomolecule aggregation.The Organic and Macromolecular Chemistry Program supports Professor Matthew Francis of the University of California- Berkeley whose research, it is anticipated, will yield fundamental insight into the use of biomolecules for materials synthesis, and the particular emphasis on protein-based structures will complement the applications for which DNA can be used. The greatest impact of the proposed research program is the unique training environment it will provide for graduate students and undergraduates. All students will combine organic synthesis, physical organic chemistry, and transition metal chemistry with the expression, purification and characterization methods associated with proteins. The students will possess a diverse set of technical skills and will be capable of solving interdisciplinary problems at the interface of chemistry and biology. Professor Francis will attempt to impact the community through a special effort to inform non-scientists about nanotechnology. He will implement a vigorous lecture series to be given at Rotary Clubs and other local organizations with the goal of describing the profound benefits of nanotechnology. Similar talks will be given at high schools in the local community.