Single Conformation Spectroscopy and Isomerization Dynamics of Synthetic Foldamers

Purdue University, West Lafayette IN

Investigators

Abstract

In this award, funded by the Experimental Physical Chemistry Program of the Division of Chemistry, Professor Timothy Zwier of Purdue University and his graduate and undergraduate students will investigate the spectroscopy and isomerization dynamics of a series of beta-peptide, gamma-peptide, and hybrid (e.g., alpha/beta) synthetic foldamers containing 2-10 residues. These molecules will be studied either as isolated neutral molecules cooled in a supersonic expansion or as ions cooled to 10 K in a cryo-cooled ion trap. The focus will be on molecules that differ from naturally-occurring alpha-peptides in having one (beta) or two (gamma) extra carbon atoms separating the amide groups, giving them additional flexibility and opening up a wider range of secondary structures that either mimic or improve on those found in nature. Professor Zwier and his team will use laser-based methods that enable them to record infrared and ultraviolet spectra of single conformations free from interference from one another, and to determine their relative populations. The results will also provide benchmark tests of the accuracy of computer models of the behavior of proteins and synthetic foldamers. Finally, lasers will be used to initiate conformational isomerization in order to determine the energies, time-scales, and energy flow associated with the isomerization process. This research project will impact society at large by providing fundamental insight to the inherent structural preferences of these synthetic foldamers, which are being applied by synthetic chemists to a wide range of biomedical and drug-discovery applications. Sam Gellman and his group at University of Wisconsin-Madison are collaborating in this study, synthesizing foldamers that test particular aspects of their behavior. The design of unique helical scaffolds tailor-made to interact with specific biological receptors requires a knowledge of, and control over, the structural preferences of the individual sub-units of which they are made. The strong collaboration with a leading synthetic group in the foldamer field ensures close-coupled feedback that will maximize the benefit of this project's results towards biomedical applications.