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Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

Thomas, Daniel A. and Sohn, Chang Ho and Gao, Jinshan and Beauchamp, J. L. (2014) Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides. Journal of Physical Chemistry A, 118 (37). pp. 8380-8392. ISSN 1089-5639. http://resolver.caltech.edu/CaltechAUTHORS:20141017-080915163

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Abstract

Free radical-initiated peptide sequencing (FRIPS) mass spectrometry derives advantage from the introduction of highly selective low-energy dissociation pathways in target peptides. An acetyl radical, formed at the peptide N-terminus via collisional activation and subsequent dissociation of a covalently attached radical precursor, abstracts a hydrogen atom from diverse sites on the peptide, yielding sequence information through backbone cleavage as well as side-chain loss. Unique free-radical-initiated dissociation pathways observed at serine and threonine residues lead to cleavage of the neighboring N-terminal C_α–C or N–C_α bond rather than the typical Cα–C bond cleavage observed with other amino acids. These reactions were investigated by FRIPS of model peptides of the form AARAAAXAA, where X is the amino acid of interest. In combination with density functional theory (DFT) calculations, the experiments indicate the strong influence of hydrogen bonding at serine or threonine on the observed free radical chemistry. Hydrogen bonding of the side-chain hydroxyl group with a backbone carbonyl oxygen aligns the singly occupied π orbital on the β-carbon and the N–C_α bond, leading to low-barrier β-cleavage of the N–C_α bond. Interaction with the N-terminal carbonyl favors a hydrogen-atom transfer process to yield stable c and z• ions, whereas C-terminal interaction leads to effective cleavage of the C_α–C bond through rapid loss of isocyanic acid. Dissociation of the C_α–C bond may also occur via water loss followed by β-cleavage from a nitrogen-centered radical. These competitive dissociation pathways from a single residue illustrate the sensitivity of gas-phase free radical chemistry to subtle factors such as hydrogen bonding that affect the potential energy surface for these low-barrier processes.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1021/jp501367w DOIArticle
http://pubs.acs.org/doi/abs/10.1021/jp501367wPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/jp501367wPublisherSupporting Information
ORCID:
AuthorORCID
Beauchamp, J. L.0000-0001-8839-4822
Additional Information:© 2014 American Chemical Society. Received: February 7, 2014; Revised: March 3, 2014; Published: March 7, 2014. The authors acknowledge Wei-Guang Liu and Prof. William A. Goddard III for their assistance and instruction in the use of software used to perform theoretical calculations as well as the Materials and Process Simulation Center at Caltech, which kindly provided computational resources. This project was funded and supported by the Beckman Institute at Caltech and in its early stages by National Science Foundation grant CHE-0416381.
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Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
NSFCHE-0416381
Record Number:CaltechAUTHORS:20141017-080915163
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141017-080915163
Official Citation:Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides Daniel A. Thomas, Chang Ho Sohn, Jinshan Gao, and J. L. Beauchamp The Journal of Physical Chemistry A 2014 118 (37), 8380-8392
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:50468
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Oct 2014 18:28
Last Modified:01 Sep 2017 20:23

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