CAREER: Electronic and stereoelectronic control of protein structure

在化学系的有机和大分子化学项目以及分子和细胞生物科学系的生物分子系统集群的支持下，特拉华大学化学系的Zondlo教授将主要研究蛋白质构象和折叠的分子控制。具体来说，他的研究将集中在立体电子控制脯氨酸构象及其对多肽和蛋白质中整体远程构象的影响。大部分的工作集中在小的、定义明确的寡肽的合成上，这些寡肽结合了特异性的、改变了的残基。结构核磁共振和CD方法被用来研究改变对构象的影响。将使用两种方法来控制蛋白质构象：(i)通过控制脯氨酸残基的环折叠来控制主链构象，（ii）通过调节脯氨酸和/或芳香环电子来控制顺-反异构化。这些方法将用于稳定多肽中的蛋白质二级结构，稳定蛋白质结构，并设计能够有条件作用的分子，在一种环境中产生一种结构或反应，在不同的环境中产生相反的结构或反应。在化学学部的有机和大分子化学项目以及分子和细胞生物科学部的生物分子系统集群的支持下，Zondlo教授将解决对疾病治疗至关重要的蛋白质构象的理解至关重要的问题。该提案还旨在开发新的控制结构和功能的工具，从而为纳米技术的新进展提供基础。该项目将对研究生和本科生进行分析和合成化学的技术和工具及其在大分子结构控制中的应用方面的重要和广泛的培训。本科生将在推进该项目的所有具体目标方面发挥重要作用，为他们未来在科学和社会中的进步和领导角色做好准备。最广泛地说，这项工作旨在通过开发针对普通受众的高中化学课程模块来提高科学家和非科学家对化学的理解水平，该课程模块教授现代化学的兴奋和应用。

With the support of the Organic and Macromolecular Chemistry Program in the Chemistry Division and the Biomolecular Systems Cluster in the Division of Molecular and Cellular Biosciences, Professor Zondlo, of the Chemistry Department at the University of Delaware, will perform research that focuses on molecular control of protein conformation and folding. Specifically, his research will focus on stereoelectonic control over proline conformations and their implications on overall long-range conformations in polypeptides and proteins. Much of the work centers on the synthesis of small well-defined oligopeptides, which incorporate specifically, altered residues. Structural NMR and CD methods are used to investigate the effects of the alterations on conformations. Two approaches to control protein conformation will be used: (i) controlling main chain conformation via controlling the ring pucker of proline residues, and, (ii) controlling cis-trans isomerization via tuning of proline and/or aromatic ring electronics. These approaches will be used to stabilize protein secondary structures in peptides, to stabilize protein structures, and to design molecules which are able to act conditionally, producing one structure or response in one environment and producing a contrary structure or response in a different environment.With the support of the Organic and Macromolecular Chemistry Program in the Chemistry Division and the Biomolecular Systems Cluster in the Division of Molecular and Cellular Biosciences, Professor Zondlo will addresses issues of fundamental importance to the understanding of protein confomation important to the treatment of disease. This proposal also aims to develop new tools for control of structure and function and will thus provide a foundation for new advances in nanotechnology. This project will involve significant and broad-based training of graduate students and undergraduate student researchers in the techniques and tools of analytical and synthetic chemistry and their application toward control of macromolecular structure. Undergraduates will be situated to play a significant role in advancing all specific aims of this project, preparing them for future advances and leadership roles in science and society. Most broadly, this work aims to elevate the level of understanding of chemistry by scientists and non-scientists by developing a curriculum module for high school chemistry, targeted for a general audience, which teaches the excitement and applications of modern chemistry.