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Structural analysis of naphthoquinone protein adducts with liquid chromatography/tandem mass spectrometry and the scoring algorithm for spectral analysis (SALSA)
Author(s) -
Zhang Fagen,
Bartels Michael J.
Publication year - 2004
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.1552
Subject(s) - chemistry , tandem mass spectrometry , chromatography , electrospray ionization , mass spectrometry , naphthoquinone , adduct , high performance liquid chromatography , liquid chromatography–mass spectrometry , valine , amino acid , biochemistry , organic chemistry
Abstract The relative reactivities of various naphthoquinone isomers (1,4‐, 1,2‐ and 2‐methyl‐1,4‐naphthoquinone) to two test proteins, apomyoglobin and human hemoglobin, were evaluated via liquid chromatography/electrospray ionization mass spectrometry (LC/ESI‐MS). The structural characterization of the resulting adducts was also obtained by LC/ESI‐MS analysis of the intact proteins. The reactive sites of apomyoglobin and human hemoglobin with 1,4‐naphthoquinone and 1,2‐naphthoquinone were also identified through characterization of adducted tryptic peptides by use of high‐pressure liquid chromatography/electrospray ionization with tandem mass spectrometry (HPLC/ESI‐MS/MS), TurboSEQUEST®, and the scoring algorithm for spectral analysis (SALSA). Four adducted peptides, which were formed by nucleophilic addition of a lysine amino acid residue to 1,4‐naphthoquinone, were also identified, as was an adducted peptide from incubation of 1,2‐naphthoquinone with apomyoglobin. In the case of incubation of human hemoglobin with the two naphthoquinones, two adducted peptides were identified from the N‐terminal valine modification of the alpha and beta chains of human hemoglobin. The adducted protein formation may imply that naphthalene produces its in vivo toxicity through 1,2‐ and 1,4‐naphthoquinone metabolites reacting with biomolecular proteins. Copyright © 2004 John Wiley & Sons, Ltd.