Nabuchi Y, Fujiwara E, Ueno K, Kuboniwa H, Asoh Y, Ushio H
Preliminary Drug Evaluation Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Pharm Res. 1995 Dec;12(12):2049-52. doi: 10.1023/a:1016281031373.
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.
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.
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.
The region around Met8 is important for the activity of the parathyroid hormone.
确定经过氧化氢处理的重组人甲状旁腺激素（rhPTH）的氧化产物、被氧化的氨基酸残基以及氧化产物的生物活性。
通过溴化氰裂解、胰蛋白酶消化及随后的快原子轰击质谱法确定氧化残基。在大鼠骨肉瘤细胞腺苷酸环化酶测定中检测每种氧化型rhPTH的生物活性。
分离出三种氧化产物，即8位甲硫氨酸（Met8）亚砜、18位甲硫氨酸（Met18）亚砜以及两个位置均为甲硫氨酸亚砜。似乎Met8和Met18的氧化形式是Met双氧化形式生成过程中的中间体。所有氧化形式的生物活性均降低，Met8氧化时的活性降低程度比Met18氧化时更明显。
Met8周围区域对甲状旁腺激素的活性很重要。
