Development of a method to investigate intra-molecular proton migration during collision induced dissociation of gas-phase peptides

Loading...
Thumbnail Image
Authors
Wu, Qun
Advisors
Van Stipdonk, Michael J.
Issue Date
2005-12
Type
Thesis
Keywords
Research Projects
Organizational Units
Journal Issue
Citation
Abstract

Use of a combination of hydrogen/deuterium (H/D) exchange, mass spectrometry (MS) and/or CID is a rapidly evolving approach to the investigation of protein structure and conformation and the dynamics of conformational change. It has been noted, however, interpretation of CID MS data on partially deuterated peptide ions can, in principle, be hampered by both inter- and intra-molecular migration of hydrogen and deuterium atoms. In this study, an isotope tracer was produced in situ by a McLafferty-type rearrangement of C-terminal peptide tert -butyl esters. This rearrangement generates a peptide with a C-terminal acid group with an isotope label. The label can then be traced through multiple CID stages to determine the amount of intra-molecular migration and scrambling of protons among exchangeable sites. Experimental results from a series of Li + cationized sarcosine substitution peptides show that the C-terminal acid and amide positions, and the amide position adjacent to the C-terminus, allow the exchange of the isotope label. Transfer to the amide position at the N-terminus, the position for which the distance from the site at which the isotope tracer was initially generated is the greatest, appears to be less favored. The influence of amino acids and cations on intramolecular proton migration was also investigated. Three series of peptides AcSarGXOtBu, AcGSarXOtBu, AcSarSarXOtBu (where X was glycine(G), alanine(A), valine(V), leucine(L), phenylalanine(F)) together with three cations Li + , Na + and Ag + were used in this study. The results show that amino acids and cations have only a slight effect on the amount of proton migration observed.

Table of Contents
Description
Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry.
"December 2005."
Publisher
Journal
Book Title
Series
PubMed ID
DOI
ISSN
EISSN