CAREER: Electronic and stereoelectronic control of protein structure

在化学系的有机和大分子化学计划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，特拉华州大学化学系的Zondlo教授将进行研究，重点是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和它们的影响，在多肽和蛋白质的整体长程构象。许多工作集中在合成小的定义明确的寡肽，其中纳入具体的，改变的残基。结构NMR和CD方法被用来研究构象的变化的影响。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褶皱来控制主链构象，和（ii）通过调节脯氨酸和/或芳环电子来控制顺-反异构化。这些方法将用于稳定肽中的蛋白质二级结构，稳定蛋白质结构，以及设计能够有条件地起作用的分子，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。在化学系有机和大分子化学计划和生物分子系统集群的支持下，分子和细胞生物科学，Zondlo教授将解决对疾病治疗重要的蛋白质构象的理解至关重要的问题。该提案还旨在开发控制结构和功能的新工具，从而为纳米技术的新进展奠定基础。该项目将涉及研究生和本科生研究人员在分析和合成化学的技术和工具及其对大分子结构控制的应用方面的重要和广泛的培训。本科生将在推进本项目的所有具体目标方面发挥重要作用，为未来的进步和科学与社会的领导作用做好准备。最广泛地说，这项工作的目的是提高科学家和非科学家对化学的理解水平，为高中化学开发一个课程模块，针对普通观众，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.