Characterization of model peptide adducts with reactive metabolites of naphthalene by mass spectrometry
Pham, NT; Jewell, WT; Morin, D; Jones, AD; Buckpitt, AR
HERO ID
1467107
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1467107 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Characterization of model peptide adducts with reactive metabolites of naphthalene by mass spectrometry |
| Authors | Pham, NT; Jewell, WT; Morin, D; Jones, AD; Buckpitt, AR |
| Journal | PLoS ONE |
| Volume | 7 |
| Issue | 8 |
| Page Numbers | e42053 |
| Abstract | Naphthalene is a volatile polycyclic aromatic hydrocarbon generated during combustion and is a ubiquitous chemical in the environment. Short term exposures of rodents to air concentrations less than the current OSHA standard yielded necrotic lesions in the airways and nasal epithelium of the mouse, and in the nasal epithelium of the rat. The cytotoxic effects of naphthalene have been correlated with the formation of covalent protein adducts after the generation of reactive metabolites, but there is little information about the specific sites of adduction or on the amino acid targets of these metabolites. To better understand the chemical species produced when naphthalene metabolites react with proteins and peptides, we studied the formation and structure of the resulting adducts from the incubation of model peptides with naphthalene epoxide, naphthalene diol epoxide, 1,2-naphthoquinone, and 1,4-naphthoquinone using high resolution mass spectrometry. Identification of the binding sites, relative rates of depletion of the unadducted peptide, and selectivity of binding to amino acid residues were determined. Adduction occurred on the cysteine, lysine, and histidine residues, and on the N-terminus. Monoadduct formation occurred in 39 of the 48 reactions. In reactions with the naphthoquinones, diadducts were observed, and in one case, a triadduct was detected. The results from this model peptide study will assist in data interpretation from ongoing work to detect peptide adducts in vivo as markers of biologic effect. |
| Doi | 10.1371/journal.pone.0042053 |
| Pmid | 22870282 |
| Wosid | WOS:000307284100044 |
| Url | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864569825&doi=10.1371%2fjournal.pone.0042053&partnerID=40&md5=fdd2d3c6ee9ccca2a173c7d8f64d1e0c |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000307284100044 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Sciences: Comprehensive Works; Epoxides; Naphthalenes; Metabolites; Protein metabolism; Cysteine; Histidine; Quinones; Cytotoxicity; N-Terminus; Mass spectrometry; Naphthalene; Amino acids; Biological effects; Data interpretation; Lesions; Scientific imaging; Peptides; Proteins; Chemical speciation; Veterinary colleges; Spectroscopy; Veterinary medicine; Mass spectroscopy; Occupational safety; Incubation; Aromatic hydrocarbons; Protein adducts; Rodents; Drug dosages; Ethanol; Adducts; Binding sites; Epithelium; Residues; Volatile hydrocarbons; Polycyclic aromatic hydrocarbons |