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Identification of covalent binding sites of ethyl 2-cyanoacrylate, methyl methacrylate and 2-hydroxyethyl methacrylate in human hemoglobin using LC/MS/MS techniques.

Jeppsson, Marina LU ; Mörtstedt, Harriet LU ; Ferrari, Giovanni LU ; Jönsson, Bo A LU and Lindh, Christian LU (2010) In Journal of Chromatography. B 878. p.2474-2482
Abstract
Acrylates are used in vast quantities, for instance in paints, adhesive glues, molding. They are potent contact allergens and known to cause respiratory hypersensitivity and asthma. Here we study ethyl 2-cyanoacrylate (ECA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). There are only limited possibilities to measure the exposure to acrylates, especially for biological monitoring. The aim of the present study was to investigate the chemical structures of adducts formed after reaction of hemoglobin (Hb) with ECA, MMA, and HEMA. This information may be used to identify adducted Hb peptides for biological monitoring of exposure to acrylates. Hb-conjugates with ECA, MMA, and HEMA were synthesized in vitro. The conjugates... (More)
Acrylates are used in vast quantities, for instance in paints, adhesive glues, molding. They are potent contact allergens and known to cause respiratory hypersensitivity and asthma. Here we study ethyl 2-cyanoacrylate (ECA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). There are only limited possibilities to measure the exposure to acrylates, especially for biological monitoring. The aim of the present study was to investigate the chemical structures of adducts formed after reaction of hemoglobin (Hb) with ECA, MMA, and HEMA. This information may be used to identify adducted Hb peptides for biological monitoring of exposure to acrylates. Hb-conjugates with ECA, MMA, and HEMA were synthesized in vitro. The conjugates were digested by trypsin and pronase E. Adducted peptides were characterized and analyzed by liquid chromatography and nano electro spray/hybrid quadrupole time-of-flight mass spectrometry (MS) as well as tandem quadrupole MS. The search for the adducted peptides was facilitated by visualizing the MS data by different computer programs. The results showed that ECA binds covalently to cysteines at the 104 position in the alpha and the position 112 in the beta-chains in Hb. MMA and HEMA bound to all the cysteines in both chains, Cys(104) in the alpha-chain and Cys(93) and 112 in the beta-chain. The full-length spectra of in un-digested Hb confirmed this binding pattern. There was no reaction with N-acetyl-l-lysine at physiological pH. The adducted peptides were possible to measure using LC/MS/MS in selected reaction monitoring mode. These peptides may be used for biological monitoring of exposure to ECA, MMA and HEMA. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chromatography. B
volume
878
pages
2474 - 2482
publisher
Elsevier
external identifiers
  • wos:000283410200003
  • pmid:20471333
  • scopus:77956881778
ISSN
1873-376X
DOI
10.1016/j.jchromb.2010.04.026
language
English
LU publication?
yes
id
694c1801-0c26-431d-9bc7-8b11b82c5121 (old id 1610237)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20471333?dopt=Abstract
date added to LUP
2010-06-02 10:19:28
date last changed
2018-06-17 04:56:54
@article{694c1801-0c26-431d-9bc7-8b11b82c5121,
  abstract     = {Acrylates are used in vast quantities, for instance in paints, adhesive glues, molding. They are potent contact allergens and known to cause respiratory hypersensitivity and asthma. Here we study ethyl 2-cyanoacrylate (ECA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). There are only limited possibilities to measure the exposure to acrylates, especially for biological monitoring. The aim of the present study was to investigate the chemical structures of adducts formed after reaction of hemoglobin (Hb) with ECA, MMA, and HEMA. This information may be used to identify adducted Hb peptides for biological monitoring of exposure to acrylates. Hb-conjugates with ECA, MMA, and HEMA were synthesized in vitro. The conjugates were digested by trypsin and pronase E. Adducted peptides were characterized and analyzed by liquid chromatography and nano electro spray/hybrid quadrupole time-of-flight mass spectrometry (MS) as well as tandem quadrupole MS. The search for the adducted peptides was facilitated by visualizing the MS data by different computer programs. The results showed that ECA binds covalently to cysteines at the 104 position in the alpha and the position 112 in the beta-chains in Hb. MMA and HEMA bound to all the cysteines in both chains, Cys(104) in the alpha-chain and Cys(93) and 112 in the beta-chain. The full-length spectra of in un-digested Hb confirmed this binding pattern. There was no reaction with N-acetyl-l-lysine at physiological pH. The adducted peptides were possible to measure using LC/MS/MS in selected reaction monitoring mode. These peptides may be used for biological monitoring of exposure to ECA, MMA and HEMA.},
  author       = {Jeppsson, Marina and Mörtstedt, Harriet and Ferrari, Giovanni and Jönsson, Bo A and Lindh, Christian},
  issn         = {1873-376X},
  language     = {eng},
  pages        = {2474--2482},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography. B},
  title        = {Identification of covalent binding sites of ethyl 2-cyanoacrylate, methyl methacrylate and 2-hydroxyethyl methacrylate in human hemoglobin using LC/MS/MS techniques.},
  url          = {http://dx.doi.org/10.1016/j.jchromb.2010.04.026},
  volume       = {878},
  year         = {2010},
}