Reactivity of Tyrosine Residues in One-Electron Oxidation of Peptides and Proteins

摘要

One-electron oxidation of proteins and peptides is relevant for numerous biological reasons. It is involved in several important diseases related to oxidative stress. Proteins represent an important target of free radicals derived from reduction of oxygen generated as a result of both normal cellular metabolism and external stimuli. The resulting oxidised protein in turn should be regarded as a new reactive entity which participates in damaging reactions and signalling (2 and references therein). Protein radical chemistry has been studied for more than 30 years, and a wealth of data has accumulated. However, knowledge is far from being complete. In this paper, we focus on two problems related to oxidative stress. First, direct oxidation of tyrosine residues by NO_2~· free radicals was studied in an octopeptide, angiotensin II (DRVYIHPF). This peptide is mainly a vasoconstricting agent. It can stimulate NO production and the NADPH oxidase system, and thus peroxynitrite formation. NO_2~· free radicals may be formed from peroxynitrite (4). The aim is to compare the results of oxidation by NO_2~· radicals to products from reaction with peroxynitrite (Cudie et al., submitted). The second aspect concerns one-electron oxidation of two proteins belonging to the family of c-type lysozymes, hen and turkey egg-white lysozymes. These two proteins differ by 7 amino acids but have very similar tertiary structures. Oxidants were OH~·and azide free radicals. They act by different mechanisms. The aim is to evaluate the impact of these differences in amino acid composition on the oxidation process.