title: Metal-Catalyzed Oxidation and Photo-oxidation of Glucagon.
abstract: The oxidation of glucagon by the H2O2/Cu(2+) system and by simulated sunlight was studied using HPLC-MS methodologies. It was found that copper ion-catalyzed oxidation is much faster in the residue 1-12 region than in photo-oxidation, but it is slower than photo-oxidation in the residue 18-29 region. This difference is due to the unique feature of the primary sequence of glucagon. The residue 1-12 region contains His-1 and Asp-9 that can bind to Cu(2+) ions and catalyze the oxidation of His-1 and Tyr-10, while the residue 18-29 region lacks these charged residues near the liable Met-27 and Trp-25 and hence no catalysis by the neighboring groups occurs. Fragment (residue 13-17) was more stable than the other regions of the peptide toward photo-oxidation because it contains only one oxidizable residue, Tyr-13. These findings may help explain the mechanism of action of glucagon and provide some hints for the development of effective anti-diabetic drug molecules and stable glucagon formulations.
authors.affiliation: Dr. J. Consulting, Atlanta, Georgia, 30341, USA. jzhang_mail04@yahoo.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005934:Glucagon / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry
chemical_list: D007004:Hypoglycemic Agents; D007477:Ions; D010087:Oxides; D003300:Copper; D005934:Glucagon; D006861:Hydrogen Peroxide; C000520:cuprous oxide
keywords: copper ion-catalyzed oxidation; drug stability; glucagon; molecular mechanism of action; photo-oxidation