Li S, Schöneich C, Wilson G S, Borchardt R T
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Pharm Res. 1993 Nov;10(11):1572-9. doi: 10.1023/a:1018960300769.
The effect of primary structure and external conditions on the oxidation of methionine to methionine sulfoxide by the ascorbate/Fe3+ system was studied in small model peptides. Degradation kinetics and yield of sulfoxide formation were dependent on the concentration of ascorbate and H+, with a maximum rate observed at pH 6-7. Phosphate buffer significantly accelerated the peptide degradation compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide was low. The oxidation could not be inhibited by the addition of EDTA. Other side products besides sulfoxide were observed, indicating the existence of various other pathways. The influence of methionine location at the C terminus, at the N terminus, and in the middle of the sequence was investigated. The presence of histidine in the sequence markedly increased the degradation rate as well as the sulfoxide production. The histidine catalysis of methionine oxidation occurred intramolecularly with a maximum enhancement of the oxidation rate and sulfoxide production when one residue was placed between the histidine and the methionine residue.
在小模型肽中研究了一级结构和外部条件对由抗坏血酸盐/Fe3+体系将甲硫氨酸氧化为甲硫氨酸亚砜的影响。亚砜形成的降解动力学和产率取决于抗坏血酸盐和H+的浓度，在pH 6 - 7时观察到最大速率。与Tris、HEPES和MOPS缓冲液相比，磷酸盐缓冲液显著加速了肽的降解；然而，亚砜的形成量较低。添加EDTA不能抑制氧化。观察到除亚砜之外的其他副产物，表明存在各种其他途径。研究了甲硫氨酸在C末端、N末端和序列中间位置的影响。序列中组氨酸的存在显著提高了降解速率以及亚砜的产生量。甲硫氨酸氧化的组氨酸催化发生在分子内，当在组氨酸和甲硫氨酸残基之间放置一个残基时，氧化速率和亚砜产生量的增强最大。
