A novel strategy for the targeted analysis of protein and peptide metabolites

Williamson, Nicholas A., Reilly, Charles, Tan, Chor-Teck, Ramarathinam, Sri-Harsha, Jones, Alun, Hunter, Christie L., Rooney, Francis R. and Purcell, Anthony W. (2011) A novel strategy for the targeted analysis of protein and peptide metabolites. Proteomics, 11 2: 183-192. doi:10.1002/pmic.201000474

Author Williamson, Nicholas A.
Reilly, Charles
Tan, Chor-Teck
Ramarathinam, Sri-Harsha
Jones, Alun
Hunter, Christie L.
Rooney, Francis R.
Purcell, Anthony W.
Title A novel strategy for the targeted analysis of protein and peptide metabolites
Journal name Proteomics   Check publisher's open access policy
ISSN 1615-9853
Publication date 2011-01
Year available 2010
Sub-type Article (original research)
DOI 10.1002/pmic.201000474
Volume 11
Issue 2
Start page 183
End page 192
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Collection year 2011
Language eng
Abstract In many biological applications such as epitope discovery or drug metabolism studies, the detection of naturally processed exogenous proteins (e.g. vaccines or peptide therapeutics) and their metabolites is frequently complicated by the presence of a complex endogenous mixture of closely related or even identical compounds. We describe a method that incorporates stable isotope labelling of the protein of interest, allowing the selective screening of the intact molecule and all metabolites using a modified precursor ion scan. This method involves monitoring the low-molecular-weight fragment ions produced during MS/MS that distinguish isotopically labelled peptides from related endogenous compounds. All isotopically labelled peptides can be selected using this method. The technique makes no assumptions about the processed or post-translational state of the peptide, and hence can selectively screen out modified peptides that would otherwise be missed by single reaction monitoring approaches. This method does not replace single reaction monitoring or regular precursor scanning techniques; instead, it is a method that can be used when the assumptions required for the former two techniques cannot be predicted. The potential for this technique to be used in metabolism and pharmacokinetic experiments is discussed with specific examples looking at the metabolism of α-synuclein in serum and the brain. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keyword Absorption, distribution, metabolism, and excretion
Drug metabolism
Immonium ion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 15 DEC 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Created: Sun, 06 Feb 2011, 00:01:36 EST