Photo- and Radiation-Induced One-Electron Oxidation of Methionine in Various Structural Environments Studied by Time-Resolved Techniques

Abstract

Oxidation of methionine (Met) is an important reaction that plays a key role in protein modifications during oxidative stress and aging. The first steps of Met oxidation involve the creation of very reactive and short-lived transients. Application of complementary time-resolved radiation and photochemical techniques (pulse radiolysis and laser flash photolysis together with time-resolved CIDNP and ESR techniques) allowed comparing in detail the one-electron oxidation mechanisms initiated either by ●OH radicals and other one-electron oxidants or the excited triplet state of the sensitizers e.g., 4-,3-carboxybenzophenones. The main purpose of this review is to present various factors that influence the character of the forming intermediates. They are divided into two parts: those inextricably related to the structures of molecules containing Met and those related to external factors. The former include (i) the protection of terminal amine and carboxyl groups, (ii) the location of Met in the peptide molecule, (iii) the character of neighboring amino acid other than Met, (iv) the character of the peptide chain (open vs cyclic), (v) the number of Met residues in peptide and protein, and (vi) the optical isomerism of Met residues. External factors include the type of the oxidant, pH, and concentration of Met-containing compounds in the reaction environment. Particular attention is given to the neighboring group participation, which is an essential parameter controlling one-electron oxidation of Met. Mechanistic aspects of oxidation processes by various one-electron oxidants in various structural and pH environments are summarized and discussed. The importance of these studies for understanding oxidation of Met in real biological systems is also addressed.

Evaluation of Hydroxyl Radical Reactivity by Thioether Group Proximity in Model Peptide Backbone: Methionine versus S-Methyl-Cysteine

“…Time-resolved kinetic studies by pulse radiolysis have expanded our mechanistic understanding of radical reactivity of Met in differently functionalized environments [ 8 ]. An overview of the transient-species detection in the one-electron oxidation of Met derivatives by various time-resolved techniques has been recently presented [ 9 ]. Mechanistic aspects of Met oxidation according to various structural characteristics given by peptide sequences and pH by one-electron oxidants (including HO • ) are summarized and discussed.…”

“…Neighboring group participation seems to be an essential interaction that controls the outcome of the one-electron oxidation of methionine. The observed transient species are precursors of the final products [ 9 ]. On the other hand, the photosensitized oxidation of Met derivatives by the excited triplet of 3-carboxybenzophenone was shown to differ significantly, leading to α-thioalkyl radical formation through an electron transfer coupled by proton transfer (ET–PT) within the encounter complex [ 10 ].…”

“…Based on these premises, here we report the study on the reactions of HO • with methionine (Met) derivative 1 , and with its congener cysteine-methylated (Cys-Me) derivative 2 under anoxic conditions ( Scheme 3 ). Both of them contain the same model peptide backbone: compound 1 represents the simplest case of a Met residue located in a peptide sequence, at the same time eliminating the known chemistry of unsubstituted Met, i.e., occurrence of intramolecular proton transfer from the amino group and decarboxylation [ 9 , 13 ]. The current reactivity comparison between compounds 1 and 2 aims at understanding the influence of the thioether group distance from the peptide backbone ( 2 has one CH 2 less) on the chemistry of HO • radical.…”

Does the Presence of Ground State Complex between a PR-10 Protein and a Sensitizer Affect the Mechanism of Sensitized Photo-Oxidation?

“…Most of the protein modifications induced by oxidants appear at amino acid side chains prone to oxidation, such as those containing sulphur (Met, Cys) or an aromatic ring (Tyr, Phe, Trp and His) [1,2]. The sensitized photo-oxidation of proteins by the excited triplet state of carboxybenzophenone ( 3 CB*) is a good example of one-electron oxidation process [3][4][5]. Carboxybenzophenone (CB) is a photosensitizer with well-established chemical, photochemical and photophysical properties [6][7][8].…”

“…3 CB* can be quenched by different amino acid side chains with different quenching rate constants and different mechanisms, such as electron transfer or energy transfer [9][10][11]. Tyr, Met and Cys quench 3 CB* by electron transfer yielding, respectively, tyrosyl radicals (TyrO • ), sulphur-centered radical cation (Met>S +• ) and thiyl radicals (CysS • ) [5,12,13]. The sulphur radical cation, Met>S +• , can interact with electron-rich atoms (such as S, O or N), yielding well characterized two-centered three-electron bonds, depending on the geometry and neighboring amino acid side chains (Scheme 1) [4,9,[14][15][16].…”