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

Chryssostomos Chatgilialoglu; Magdalena Grzelak; Konrad Skotnicki; Piotr Filipiak; Franciszek Kazmierczak; Gordon L Hug; Krzysztof Bobrowski; Bronislaw Marciniak

doi:10.3390/ijms23126550

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

Int J Mol Sci. 2022 Jun 11;23(12):6550. doi: 10.3390/ijms23126550.

Authors

Chryssostomos Chatgilialoglu^{1

2}, Magdalena Grzelak¹, Konrad Skotnicki³, Piotr Filipiak^{1

4}, Franciszek Kazmierczak⁴, Gordon L Hug⁵, Krzysztof Bobrowski³, Bronislaw Marciniak^{1

4}

Affiliations

¹ Center for Advanced Technology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 10, 61-614 Poznan, Poland.
² ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy.
³ Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
⁴ Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznanskiego 8, 61-614 Poznan, Poland.
⁵ Radiation Laboratory, University of Notre Dame, Notre Dame, IN 46556, USA.

Abstract

Hydroxyl radicals (HO^•) have long been regarded as a major source of cellular damage. The reaction of HO^• with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CH₃C(O)NHCHXC(O)NHCH₃, where X = CH₂CH₂SCH₃ or CH₂SCH₃, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC-MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals.

Keywords: S-methyl-cysteine; free radicals; high-resolution MS/MS; methionine; oxidation; pulse and γ-radiolysis.

MeSH terms

Cysteine
Hydroxyl Radical* / chemistry
Methionine* / chemistry
Oxidation-Reduction
Peptides / chemistry
Pulse Radiolysis
Sulfides
Tandem Mass Spectrometry

Substances

Peptides
Sulfides
Hydroxyl Radical
Methionine
Cysteine

Grants and funding

This research was funded by the National Science Centre, Poland, project no. UMO-2017/27/B/ST4/00375 and by statutory funds of the Institute of Nuclear Chemistry and Technology (INCT) (K.B. and K.S.).