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

Jeppsson, Marina LU ; Jönsson, Bo ; Kåredal, Monica LU orcid and Lindh, Christian LU orcid (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)
Please use this url to cite or link to this publication:
author
; ; and
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 (ACS)
external identifiers
  • wos:000260964700012
  • pmid:18831565
  • scopus:57449097765
  • pmid:18831565
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
2016-04-04 08:32:59
date last changed
2022-01-29 03:32:14
@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 (ACS)}},
  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}},
  doi          = {{10.1021/tx800242j}},
  volume       = {{Oct 3}},
  year         = {{2008}},
}