Synthesis and characterization of peptide adducts for use in monitoring human exposure to acrylonitrile and ethylene oxide.
Human exposure to ethylene oxide and acrylonitrile may be monitored by determination of the products that these electrophilic compounds form with the amino terminal of hemoglobin.
The procedure involves a modified Edman degradation, using the reagent pentafluorophenyl isothiocyanate, which cleaves the adducted N-terminal amino acid from the protein chain as a substituted pentafluorophenyl thiohydantoin.
This may then be quantitated using selected ion monitoring gas chromatographymass spectrometry (GC-MS).
To overcome problems arising from the lack of an ideal internal standard for this analysis, we have now synthesized adducts of ethylene oxide and acrylonitrile with the N-terminal tripeptide of the a-chain of human globin (Val-Leu-Ser).
These adducts should behave analogously to the protein adduct in the Edman degradation.
The adducts were characterized by nuclear magnetic resonance and fast atom bombardment and electrospray MS and tandem MS.
Additionally, an analogous stable isotope-labeled standard was synthesized for the acrylonitrile adduct using a d8-labeled tripeptide.
Quantitative calibration lines for analysis of the adducts have been established and the validity of the assays established by the detection of acrylonitrile adducts in the globin of acrylonitrile-exposed workers and of cigarette smokers.
Mots-clés Pascal : Acrylonitrile, Oxirane, Exposition professionnelle, Homme, Médecine travail, Surveillance biologique, Adduit moléculaire, Hémoglobine, Peptide, Tabagisme, Carcinogène, Sang, Liquide biologique
Mots-clés Pascal anglais : Acrylonitrile, Ethylene oxide, Occupational exposure, Human, Occupational medicine, Biological monitoring, Molecular adduct, Hemoglobin, Peptides, Tobacco smoking, Carcinogen, Blood, Biological fluid
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 97-0177182
Code Inist : 002B03L06. Création : 21/05/1997.