Collaborative Research: Intrinsic Gas-phase Properties of Amino Acids and Peptides: Thermochemistry, Fragmentation Mechanisms, H/D exchange and IRMPD Spectroscopy.

College Of William And Mary, Williamsburg VA

Investigators

Abstract

With this award, the Chemical Structure, Dynamics and Mechanisms program is supporting the collaborative research of Professor John C. Poutsma at the College of William and Mary and Professor Jennifer Poutsma at Old Dominion University. Professor John Poutsma employs mass spectrometry-based experiments to study the subtle interplay between the structure of amino acids and their gas-phase energetic properties. He is studying a class of compounds known as non-proteinogenic amino acids (NPAA), which are found naturally in plants and fungi, but are not used in protein synthesis. Many NPAAs are toxic to humans and other animals in part due to structural similarity to one or more of the twenty common protein amino acids (PAA). NPAAs can compete with PAAs in a variety of biological pathways including being mis-incorporated into proteins and peptides. These experiments will further understanding of the intrinsic chemistry of NPAAs as isolated entities and when incorporated into small peptides. Professor Jennifer Poutsma is performing density functional theory calculations that support and guide the experimental studies. Both research programs integrate research and educational components through the training of undergraduate researchers. The vast majority of the research projects outlined in this proposal are being performed by undergraduates at William and Mary and Old Dominion University. Performing independent research helps expose these students to the modern research in biologically relevant, mechanistic mass spectrometry, supported by advanced computational chemistry. In this research, the intrinsic gas-phase thermochemical properties of di-peptides are being determined using the extended kinetic method in a triple quadrupole instrument. Specifically, the PIs are studying the gas-phase acid-base chemistry of dipeptides that contain proline or one of its non-protein amino acid analogs azetidine-2-carboxylic acid or pipecolic acid. Absolute gas-phase thermochemical properties will be determined using the extended kinetic method (EKM) in a TSQ Quantum triple-quadrupole instrument. The collaborative research team is working to determine the effects of ring-size and conformational flexibility on the acid-base properties of these species with the goal of applying this knowledge toward a better understanding the mechanisms for selective fragmentations in low-energy tandem mass spectrometry experiments of proline-containing peptides. Peptides containing these 4- and 6-ring analogues of proline, a typical beta-turn-forming amino acid are of considerable interest in chemical biology and peptide design circles. The results of these studies are likely to be of interest to scientists in these communities.