CAREER: Electronic and stereoelectronic control of protein structure

University Of Delaware, Newark DE

Investigators

Abstract

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.