Document Detail

Selective collision-induced fragmentation of ortho-hydroxybenzyl-aminated lysyl-containing tryptic peptides.
MedLine Citation:
PMID:  23765610     Owner:  NLM     Status:  In-Data-Review    
RATIONALE: In protein studies that employ tandem mass spectrometry the manipulation of protonated peptide fragmentation through exclusive dissociation pathways may be preferred in some applications over the comprehensive amide backbone fragmentation that is typically observed. In this study, we characterized the selective cleavage of the side-chain Cζ -Nε bond of peptides with ortho-hydroxybenzyl-aminated lysine residues.
METHODS: Internal lysyl residues of representative peptides were derivatized via reductive amination with ortho-hydroxybenzaldehyde. The modified peptides were analyzed using collision-induced dissociation (CID) on an Orbitrap tandem mass spectrometer. Theoretical calculations using computational methods (density functional theory) were performed to investigate the potential dissociation mechanisms for the Cζ -Nε bond of the derivatized lysyl residue resulting in the formation of the observed product ions.
RESULTS: Tandem mass spectra of the derivatized peptide ions exhibit product peaks corresponding to selective cleavage of the side-chain Cζ -Nε bond that links the derivative to lysine. The ortho-hydroxybenzyl derivative is released either as a neutral moiety [C7 H6 O1 ] or as a carbocation [C7 H7 O1 ](+) through competing pathways (retro-Michael versus Carbocation Elimination (CCE), respectively). The calculated transition state activation barriers indicate that the retro-Michael pathway is kinetically favored over CCE and both are favored over amide cleavage.
CONCLUSIONS: The application of ortho-hydroxybenzyl amination is a promising peptide derivatization scheme for promoting selective dissociation pathways in the tandem mass spectrometry of protonated peptides. This can be implemented in the rational development of peptide reactive reagents for applications that may benefit from selective fragmentation paths (including crosslinking or MRM reagents). Copyright © 2013 John Wiley & Sons, Ltd.
E S Simon; P G Papoulias; P C Andrews
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  27     ISSN:  1097-0231     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  1619-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 John Wiley & Sons, Ltd.
Departments of Biological Chemistry, Bioinformatics, and Chemistry, University of Michigan, Ann Arbor, 48103.
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