PURPOSE: To determine the oxidation products of recombinant human parathyroid hormone (rhPTH) treated with H2O2, the amino acid residue oxidized, and the biological activity of the oxidation products. METHODS: Oxidized residues were determined by CNBr cleavage, trypsin digestion and subsequent fast atom bombardment mass spectrometry. The biological activity of each oxidized rhPTH was examined in rat osteosarcoma cell adenylate cyclase assay. RESULTS: Three oxidized products were isolated, namely, Met at position 8 (Met8) sulfoxide, Met at position 18 (Met18) sulfoxide and both positions Met sulfoxide. It appears that the Met8 and Met18 oxidized forms are intermediates in the generation of the Met doubly oxidized form. All oxidized forms possessed reduced biological activity, more so for oxidation at Met8 than at Met18. CONCLUSIONS: The region around Met8 is important for the activity of the parathyroid hormone.
PURPOSE: To determine the oxidation products of recombinant humanparathyroid hormone (rhPTH) treated with H2O2, the amino acid residue oxidized, and the biological activity of the oxidation products. METHODS: Oxidized residues were determined by CNBr cleavage, trypsin digestion and subsequent fast atom bombardment mass spectrometry. The biological activity of each oxidized rhPTH was examined in ratosteosarcoma cell adenylate cyclase assay. RESULTS: Three oxidized products were isolated, namely, Met at position 8 (Met8) sulfoxide, Met at position 18 (Met18) sulfoxide and both positions Met sulfoxide. It appears that the Met8 and Met18 oxidized forms are intermediates in the generation of the Met doubly oxidized form. All oxidized forms possessed reduced biological activity, more so for oxidation at Met8 than at Met18. CONCLUSIONS: The region around Met8 is important for the activity of the parathyroid hormone.
Authors: T J Gardella; D Rubin; A B Abou-Samra; H T Keutmann; J T Potts; H M Kronenberg; S R Nussbaum Journal: J Biol Chem Date: 1990-09-15 Impact factor: 5.157
Authors: Jin Yin; Jhih-Wei Chu; Margaret Speed Ricci; David N Brems; Daniel I C Wang; Bernhardt L Trout Journal: Pharm Res Date: 2005-01 Impact factor: 4.200
Authors: Gang Cao; Kyu Pil Lee; Jenny van der Wijst; Mark de Graaf; Annemiete van der Kemp; René J M Bindels; Joost G J Hoenderop Journal: J Biol Chem Date: 2010-06-28 Impact factor: 5.157
Authors: Jin Yin; Jhih-Wei Chu; Margaret Speed Ricci; David N Brems; Daniel I C Wang; Bernhardt L Trout Journal: Pharm Res Date: 2004-12 Impact factor: 4.200