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Identification of Covalent Binding Sites of Phthalic Anhydride in Human Hemoglobin.

Jeppsson, Marina LU ; Jönsson, Bo; Kåredal, Monica LU and Lindh, Christian LU (2008) In Chemical Research in Toxicology Oct 3. p.2156-2163
Abstract
Phthalic anhydride (PA) is a reactive low molecular weight compound used in the chemical industry. The exposure of PA may lead to work-related airway diseases such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an increase in hapten-specific IgG antibodies in workers but with a low presence of specific IgE antibodies. In this study, the binding of PA to human hemoglobin (Hb) in vitro was investigated. Trypsin and Pronase E digestion, LC, LC/MS/MS, GC/MS analysis, and nanoelectrospray hybrid quadrupole time-of-flight MS were used to identify the adducted amino acids of the synthesized PA-Hb conjugates. In the conjugate with the molar ratio 1:0.1, a total of six adducted amino acids were identified. N-Terminal valine... (More)
Phthalic anhydride (PA) is a reactive low molecular weight compound used in the chemical industry. The exposure of PA may lead to work-related airway diseases such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an increase in hapten-specific IgG antibodies in workers but with a low presence of specific IgE antibodies. In this study, the binding of PA to human hemoglobin (Hb) in vitro was investigated. Trypsin and Pronase E digestion, LC, LC/MS/MS, GC/MS analysis, and nanoelectrospray hybrid quadrupole time-of-flight MS were used to identify the adducted amino acids of the synthesized PA-Hb conjugates. In the conjugate with the molar ratio 1:0.1, a total of six adducted amino acids were identified. N-Terminal valine was found adducted in both the alpha- and the beta-chains as well as a total of four lysines, Val 1, Lys 16, and Lys 61 on the alpha-chain and Val 1, Lys 66, and Lys 144 on the beta-chain. Two types of lysine adducts were found, a phthalamide and a phthalimide. It was also found that PA differs in its binding site as compared to hexahydrophthalic anhydride. The result of this study suggests several interesting applications of biological monitoring. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Chemical Research in Toxicology
volume
Oct 3
pages
2156 - 2163
publisher
The American Chemical Society
external identifiers
  • wos:000260964700012
  • pmid:18831565
  • scopus:57449097765
ISSN
1520-5010
DOI
10.1021/tx800242j
language
English
LU publication?
yes
id
4114f200-7939-40fc-9153-e227a17ba544 (old id 1262633)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18831565?dopt=Abstract
date added to LUP
2008-11-06 15:02:56
date last changed
2017-01-01 07:37:05
@article{4114f200-7939-40fc-9153-e227a17ba544,
  abstract     = {Phthalic anhydride (PA) is a reactive low molecular weight compound used in the chemical industry. The exposure of PA may lead to work-related airway diseases such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an increase in hapten-specific IgG antibodies in workers but with a low presence of specific IgE antibodies. In this study, the binding of PA to human hemoglobin (Hb) in vitro was investigated. Trypsin and Pronase E digestion, LC, LC/MS/MS, GC/MS analysis, and nanoelectrospray hybrid quadrupole time-of-flight MS were used to identify the adducted amino acids of the synthesized PA-Hb conjugates. In the conjugate with the molar ratio 1:0.1, a total of six adducted amino acids were identified. N-Terminal valine was found adducted in both the alpha- and the beta-chains as well as a total of four lysines, Val 1, Lys 16, and Lys 61 on the alpha-chain and Val 1, Lys 66, and Lys 144 on the beta-chain. Two types of lysine adducts were found, a phthalamide and a phthalimide. It was also found that PA differs in its binding site as compared to hexahydrophthalic anhydride. The result of this study suggests several interesting applications of biological monitoring.},
  author       = {Jeppsson, Marina and Jönsson, Bo and Kåredal, Monica and Lindh, Christian},
  issn         = {1520-5010},
  language     = {eng},
  pages        = {2156--2163},
  publisher    = {The American Chemical Society},
  series       = {Chemical Research in Toxicology},
  title        = {Identification of Covalent Binding Sites of Phthalic Anhydride in Human Hemoglobin.},
  url          = {http://dx.doi.org/10.1021/tx800242j},
  volume       = {Oct 3},
  year         = {2008},
}