Molecular Level Understanding of Dissociation of Radical Cationic Glycosylated and Phosphorylated Peptides: Energetics, Dynamics and Mechanisms
EMSL Project ID
40004
Abstract
The goal of this proposed project is to achieve a fundamental understanding of the mechanisms, energetics, and kinetics of specific dissociation pathways of the radical cations of post-translationally modified peptides in the gas phase; particular emphasis will be placed on glycopeptides and phosphorylated peptides - two important and common protein post-translational modifications - using a combination of experimental and computational approaches. Understanding their dissociation mechanisms will provide the scientific basis underlying the establishment of gas phase peptide sequencing strategies, which are at the core of the emerging field of proteomics; the general rules governing the dissociations of peptide radical cations remain poorly understood. In the initial stage, we aim to generate radical cationic glycopeptides and phosphorylated peptides building upon established approaches from our previous projects. As far as we know, no studies have involved explorations of the formation of molecular radical post-translationally modified peptide cations. In this proposed study, a range of phosphopeptide radical cationic systems will be designed, prepared, and characterized to deduce their gas phase chemistry using a combination of higher collision-induced dissociation (HCD) experiments in the LTQ/Orbitrap, surface-induced dissociation experiments in FTICR with Rice-Ramsperger-Kassel-Marcus and density functional theory calculations. The specific goals are (a) to dissect systematically the Ca-C, Calpha-Cbeta, and phosphate ester bonds of peptide radical cations; (b) to elucidate factors that account for the structures, energetics, and kinetics of these individual fragmentation pathways; and (c) to examine the mechanistic roles that the location of the radical site and the basicity of amino acid residues and hydroxyl groups have on the dissociation of phosphorylated peptide radical cations.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2010-10-01
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Chu IK, and J Laskin. 2011. "Review: Formation of Peptide Radical Ions Through Dissociative Electron Transfer in Ternary Metal-Ligand-Peptide Complexes." European Journal of Mass Spectrometry 17(6):543-556. doi:10.1255/ejms.1156
Laskin J, R Kong, T Song, and IK Chu. 2012. "Effect of the Basic Residue on the Energetics and Dynamics of Dissociation of Phosphopeptides." International Journal of Mass Spectrometry 330-332:295-301.
Laskin J, Z Yang, C Lam, and IK Chu. 2012. "Energy and Entropy Effects in Dissociation of Peptide Radical Anions." International Journal of Mass Spectrometry 316-318:251-258. doi:10.1016/j.ijms.2012.01.006
Laskin J, Z Yang, T Song, C Lam, and IK Chu. 2010. "Effect of the Basic Residue on the Energetics, Dynamics and Mechanisms of Gas- Phase Fragmentation of Protonated Peptides." Journal of the American Chemical Society 132(45):16006-16016. doi:10.1021/ja104438z
Song T, IK Chu, CK Siu, and J Laskin. 2012. "Mechanistic Examination of C?–C? Bond Cleavages of Tryptophan Residues during Dissociations of Molecular Peptide Radical Cations." PNNL-SA-87221, Pacific Northwest National Laboratory, Richland, WA.