Regular ArticleIdentification of Covalent Adducts to Protein Sulfur Nucleophiles by Alkaline Permethylation
References (0)
Cited by (41)
Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac
2017, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :After this period, intermediates as cysteine-glutamic acid- and cysteine-glycine S-conjugates were not detected. As expected no cysteine S-conjugates were found, due by the facile beta-elimination of cysteine conjugates in strong alkaline conditions [29,30]. To validate the novel method for quantification of GSH-conjugates, first standard curves of commercially available S-propyl-, S-hexyl- and S-nonyl GSH were prepared from gravimetrically prepared stock solutions.
Detection of protein adduction derived from styrene oxide to cysteine residues by alkaline permethylation
2010, Analytical BiochemistryFilling and mining the reactive metabolite target protein database
2009, Chemico-Biological InteractionsCitation Excerpt :Starting in the 1990s, success in this area was greatly aided by continuing improvements in NMR field strength (resolution) and sensitivity, and by the development of quadrupole mass filters and time-of-flight mass analyzers, techniques for soft ionization of delicate molecules including electrospray and matrix-assisted laser desorption ionization (MALDI), and the development of hybrid tandem mass spectrometers for MS/MS analysis of complex polar molecules including intact proteins. As noted above, chemical degradation of adducted proteins using acid, base, Raney nickel or protease enzymes often released small, chemically stable, adduct-derived molecules amenable to isolation and structure elucidation using ordinary organic chemical techniques [20,21]. Eventually, many reactive metabolites even yielded to chemical synthesis.
Inhibition of the calcineurin-NFAT interaction by small organic molecules reflects binding at an allosteric site
2005, Journal of Biological ChemistryCitation Excerpt :Steric and other constraints in the protein might favor products that differ from those of the reaction with synthetic peptide discussed in the legend to Fig. 7. For example, the INCA2 linkage to protein could involve a thioether bond, as observed in quinone cofactors of some amine dehydrogenases (44, 45) and as inferred for many other protein-quinone adducts (42, 43, 46-49), or an ipso adduct at the imine carbon, as observed in the complex of N-acetyl-p-quinoneimine with papain (50). Cysteinyl-quinone thioether adducts are themselves highly reactive when in the oxidized form (51) and could undergo further reactions following initial adduct formation.
Measurement of hemoglobin and albumin adducts of naphthalene-1,2-oxide, 1,2-naphthoquinone and 1,4-naphthoquinone after administration of naphthalene to F344 rats
2002, Chemico-Biological InteractionsCitation Excerpt :Covalent binding of total reactive metabolites to various tissues and proteins has been studied using radiochemical and immunochemical assays [20–23]. Alkaline permethylation of proteins followed by gas chromatography–mass spectrometry (GC–MS), first introduced by Slaughter and Hanzlik [24,25], has been used to measure specific cysteinyl adducts of naphthalene in vitro [17]. However, this assay has not been extended to in vivo studies, probably because of limited sensitivity.
Drug–protein adducts: past, present, and future
2020, Medicinal Chemistry Research