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Mass spectrometric characterization of human hemoglobin adducts formed in vitro by hexahydrophthalic anhydride.

Kåredal, Monica LU ; Jönsson, Bo A LU and Lindh, Christian LU (2002) In Chemical Research in Toxicology 15(4). p.562-569
Abstract
Primary structural information of anhydride binding to endogenous proteins is of interest in order to determine the mechanism causing the type-I allergy seen in many anhydride-exposed workers. In addition, studies on specific protein adducts may generate new methods for biological monitoring. In this study, the binding of hexahydrophthalic anhydride (HHPA) to human hemoglobin (Hb) in vitro was investigated. The in vitro synthesized conjugates were analyzed using a hybrid quadrupole-time-of-flight mass spectrometer (Q-TOF) with electrospray ionization (ESI) to determine the number of HHPA adducts per Hb molecule. Structural information on the locations of the adducts was obtained through nanospray Q-TOF, liquid chromatography-ESI mass... (More)
Primary structural information of anhydride binding to endogenous proteins is of interest in order to determine the mechanism causing the type-I allergy seen in many anhydride-exposed workers. In addition, studies on specific protein adducts may generate new methods for biological monitoring. In this study, the binding of hexahydrophthalic anhydride (HHPA) to human hemoglobin (Hb) in vitro was investigated. The in vitro synthesized conjugates were analyzed using a hybrid quadrupole-time-of-flight mass spectrometer (Q-TOF) with electrospray ionization (ESI) to determine the number of HHPA adducts per Hb molecule. Structural information on the locations of the adducts was obtained through nanospray Q-TOF, liquid chromatography-ESI mass spectrometric analysis, and gas chromatography/mass spectrometric analysis of Pronase E and tryptic digests. Up to six adducts were found on the alpha-chain and five on the beta-chain. The HHPA-adducts were localized to the N-terminal valine of the alpha- and beta-chains of Hb and to lysine residues at positions 7, 11, 16, and 40 of the alpha-chain and 8, 17, 59, 66, and 144 of the beta-chain. These results will constitute a basis for studies on structure-activity relationships as well as for development of methods for biological monitoring of acid anhydrides. (Less)
Please use this url to cite or link to this publication:
author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Nanotechnology, Phthalic Anhydrides : metabolism, Phthalic Anhydrides : pharmacology, Spectrometry, Mass, Electrospray Ionization, Matrix-Assisted Laser Desorption-Ionization, In Vitro, Human, Hemoglobins : metabolism, Erythrocytes : metabolism, Erythrocytes : drug effects
in
Chemical Research in Toxicology
volume
15
issue
4
pages
562 - 569
publisher
The American Chemical Society
external identifiers
  • wos:000175085000013
  • pmid:11952343
  • scopus:0036229470
ISSN
1520-5010
DOI
10.1021/tx0155911
language
English
LU publication?
yes
id
aefd01d2-e431-4557-bff7-f280b572948a (old id 107645)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11952343&dopt=Abstract
date added to LUP
2007-07-12 09:28:32
date last changed
2017-01-01 05:16:40
@article{aefd01d2-e431-4557-bff7-f280b572948a,
  abstract     = {Primary structural information of anhydride binding to endogenous proteins is of interest in order to determine the mechanism causing the type-I allergy seen in many anhydride-exposed workers. In addition, studies on specific protein adducts may generate new methods for biological monitoring. In this study, the binding of hexahydrophthalic anhydride (HHPA) to human hemoglobin (Hb) in vitro was investigated. The in vitro synthesized conjugates were analyzed using a hybrid quadrupole-time-of-flight mass spectrometer (Q-TOF) with electrospray ionization (ESI) to determine the number of HHPA adducts per Hb molecule. Structural information on the locations of the adducts was obtained through nanospray Q-TOF, liquid chromatography-ESI mass spectrometric analysis, and gas chromatography/mass spectrometric analysis of Pronase E and tryptic digests. Up to six adducts were found on the alpha-chain and five on the beta-chain. The HHPA-adducts were localized to the N-terminal valine of the alpha- and beta-chains of Hb and to lysine residues at positions 7, 11, 16, and 40 of the alpha-chain and 8, 17, 59, 66, and 144 of the beta-chain. These results will constitute a basis for studies on structure-activity relationships as well as for development of methods for biological monitoring of acid anhydrides.},
  author       = {Kåredal, Monica and Jönsson, Bo A and Lindh, Christian},
  issn         = {1520-5010},
  keyword      = {Nanotechnology,Phthalic Anhydrides : metabolism,Phthalic Anhydrides : pharmacology,Spectrometry,Mass,Electrospray Ionization,Matrix-Assisted Laser Desorption-Ionization,In Vitro,Human,Hemoglobins : metabolism,Erythrocytes : metabolism,Erythrocytes : drug effects},
  language     = {eng},
  number       = {4},
  pages        = {562--569},
  publisher    = {The American Chemical Society},
  series       = {Chemical Research in Toxicology},
  title        = {Mass spectrometric characterization of human hemoglobin adducts formed in vitro by hexahydrophthalic anhydride.},
  url          = {http://dx.doi.org/10.1021/tx0155911},
  volume       = {15},
  year         = {2002},
}