Li, Xiaojuan, Cournoyer, Jason J., Lin, Cheng and O'Connor, Peter B.. (2008) Use of 18O Labels to monitor deamidation during protein and peptide sample processing. Journal of The American Society for Mass Spectrometry, Vol.19 (No.6). pp. 855-864. ISSN 1044-0305

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Abstract

Nonenzymatic deamidation of asparagine residues in proteins generates aspartyl (Asp) and isoaspartyl (isoAsp) residues via a succinimide intermediate in a neutral or basic environment. Electron capture dissociation (ECD) can differentiate and quantify the relative abundance of these isomeric products in the deamidated proteins. This method requires the proteins to be digested, usually by trypsin, into peptides that are amenable to ECD. ECD of these peptides can produce diagnostic ions for each isomer; the c · + 58 and z − 57 fragment ions for the isoAsp residue and the fragment ion ((M + nH)(n−1)+· − 60) corresponding to the side-chain loss from the Asp residue. However, deamidation can also occur as an artifact during sample preparation, particularly when using typical tryptic digestion protocols. With 18O labeling, it is possible to differentiate deamidation occurring during trypsin digestion which causes a +3 Da (18O1 + 1D) mass shift from the pre-existing deamidation, which leads to a +1-Da mass shift. This paper demonstrates the use of 18O labeling to monitor three rapidly deamidating peptides released from proteins (calmodulin, ribonuclease A, and lysozyme) during the time course of trypsin digestion processes, and shows that the fast (∼4 h) trypsin digestion process generates no additional detectable peptide deamidations.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Deamination, Tandem mass spectrometry, Proteins -- Deamination, Peptides -- Analysis, Proteomics
Journal or Publication Title:	Journal of The American Society for Mass Spectrometry
Publisher:	Springer New York LLC
ISSN:	1044-0305
Date:	2008
Volume:	Vol.19
Number:	No.6
Number of Pages:	10
Page Range:	pp. 855-864
Identification Number:	10.1016/j.jasms.2008.02.011
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	National Institutes of Health (U.S.) (NIH), National Institute of General Medical Sciences (U.S.) (NIGMS), National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (U.S.) (NCRR), MDS Sciex, Petroleum Research Fund
Grant number:	P41RR10888 (NIH/NCRR), N01HV28178 (NIH/NHLBI), R01GM078293 (NIH/NIGMS)
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URI:	http://wrap.warwick.ac.uk/id/eprint/40625

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