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Michael addition of acrolein to lysinyl and N‐terminal residues of a model peptide: targets for cytoprotective hydrazino drugs
Author(s) -
Kaminskas Lisa M.,
Pyke Simon M.,
Burcham Philip C.
Publication year - 2007
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2945
Subject(s) - acrolein , chemistry , adduct , lysine , residue (chemistry) , peptide , mass spectrometry , aldehyde , tandem mass spectrometry , electrospray ionization , michael reaction , stereochemistry , chromatography , organic chemistry , biochemistry , amino acid , catalysis
The antihypertensive drug hydralazine blocks acrolein‐mediated toxicity by trapping both free aldehyde‐ and acrolein‐adducted proteins, with the latter property more closely related to cytoprotection in cellular models. Here we report the identification of products from ‘protein adduct‐trapping’ reactions using electrospray ionisation mass spectrometry (ESI‐MS). Reaction of a 13‐residue peptide containing a single lysine with acrolein for 30 min generated ions corresponding to mono ‐ and bis ‐Michael‐adducted peptides. An ion corresponding to a cyclic species formed from bis ‐adducted lysine was conspicuous at later times (60, 180 min). Tandem mass spectrometric (MS/MS) analysis revealed Michael adduction also occurred on the N‐terminus, with a novel N‐terminal (3‐formyl‐3,4‐dehydropiperidino) species formed on this residue. Addition of hydralazine to acrolein‐adducted peptides generated a diverse range of hydrazones that were also characterised by MS/MS analysis. The results confirm that mass spectrometry is a powerful tool for characterising the reactions of noxious electrophiles with biological macromolecules. Copyright © 2007 John Wiley & Sons, Ltd.