The effect of neighboring amino acid residues and solution environment on the oxidative stability of tyrosine in small peptides

被引：1

作者：

Zhang J. ^{[1
]}

Kalonia D.S. ^{[1
]}

机构：

[1] Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs

来源：

AAPS PharmSciTech | / 8卷 / 4期

关键词：

Antioxidants; Charge-effect; Ionic strength; Kinetics; Oxidation; Tyrosine;

D O I：

10.1208/pt0804102

中图分类号：

学科分类号：

摘要：

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 photo-reaction was dependent on tyrosyl pKa, 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.

引用

共 34 条

[1]

Survey Report

[2]

Wang W., Instability, stabilization, and formulation of liquid protein pharmaceuticals, Int J Pharm, 185, pp. 129-188, (1999)

[3]

Penner M.H., Yamasaki R.B., Osuga D.T., Babin D.R., Meares C.F., Feeney R.E., Comparative oxidations of tyrosines and methionines in transferrins: Human serum transferring, human lactotransferrin, and chicken ovotransferrin, Arch Biochem Biophys, 225, pp. 740-747, (1983)

[4]

Stadtman E.R., Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions, Annu Rev Biochem, 62, pp. 797-821, (1993)

[5]

Li S., Schoneich C., Borchardt R.T., Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and strategies for stabilization, Biotechnol Bioeng, 48, pp. 490-500, (1995)

[6]

Wang Y.J., Hanson M.A., Parenteral formulations of proteins and peptides: Stability and stabilizers, (1998)

[7]

Kerwin Jr B.A., Remmele Jr. R.L., Protect from light: Photodegradation and protein biologics, J Pharm Sci, 96, pp. 1468-1479, (2007)

[8]

Creed D., The photophysics and photochemistry of the near-UV absorbing amino acids. II. Tyrosine and its simple derivatives, Photochem Photobiol, 39, pp. 563-575, (1984)

[9]

Joshi P., Carraro C., Pathak M., Involvement of reactive oxygen species in the oxidation of tyrosine and dopa to melanin and in skin tanning, Biochem Biophys Res Commun, 142, pp. 265-274, (1987)

[10]

Huggins T.G., Wells-Knecht M.C., Detorie N.A., Baynes J.W., Thorpe S.R., Formation of o-tyrosine and dityrosine in protein during radiolytic and metal-catalyzed oxidation, J Biol Chem, 268, pp. 12341-12347, (1993)

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