Zhang Jian, Kalonia Devendra S
Department of Pharmaceutical Science, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
AAPS PharmSciTech. 2007 Dec 7;8(4):E102. doi: 10.1208/pt0804102.
The effects of neighboring residues and formulation variables on tyrosine oxidation were investigated in model dipeptides (glysyl tyrosine, N-acetyl tyrosine, glutamyl tyrosine, and tyrosyl arginine) and tripeptide (lysyl tyrosyl lysine). The tyrosyl peptides were oxidized by light under alkaline conditions by a zero-order reaction. The rate of the photoreaction was dependent on tyrosyl pK(a), which was perturbed by the presence of neighboring charged amino acid residues. The strength of light exposure, oxygen headspace, and the presence of cationic surfactant, cetyltrimethylammonia chloride had a significant effect on the kinetics of tyrosyl photo-oxidation. Tyrosine and model tyrosyl peptides were also oxidized by hydrogen peroxide/metal ions at neutral pH. Metal-catalyzed oxidation followed first-order kinetics. Adjacent negatively charged amino acids accelerated tyrosine oxidation owing to affinity of the negative charges to metal-ions, whereas positively charged amino acid residues disfavored the reaction. The oxidation of tyrosine in peptides was greatly affected by the presence of adjacent charged residues, and the extent of the effect depended on the solution environment.
在模型二肽（甘氨酰酪氨酸、N-乙酰酪氨酸、谷氨酰酪氨酸和酪氨酰精氨酸）和三肽（赖氨酰酪氨酰赖氨酸）中研究了相邻残基和制剂变量对酪氨酸氧化的影响。酪氨酰肽在碱性条件下通过零级反应被光氧化。光反应速率取决于酪氨酰pK(a)，其会因相邻带电氨基酸残基的存在而受到干扰。光照强度、氧气顶空以及阳离子表面活性剂十六烷基三甲基氯化铵的存在对酪氨酰光氧化动力学有显著影响。酪氨酸和模型酪氨酰肽在中性pH下也会被过氧化氢/金属离子氧化。金属催化氧化遵循一级动力学。相邻的带负电荷氨基酸由于负电荷对金属离子的亲和力而加速酪氨酸氧化，而带正电荷的氨基酸残基则不利于该反应。肽中酪氨酸的氧化受到相邻带电残基存在的极大影响，且影响程度取决于溶液环境。
