Biomimetic Radical Chemistry and Applications

Chatgilialoglu, Chryssostomos

doi:10.3390/molecules27072042

Molecules

2022

DOI: 10.3390/molecules27072042

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Biomimetic Radical Chemistry and Applications

Chryssostomos Chatgilialoglu

Abstract: Some of the most interesting aspects of free radical chemistry that emerged in the last two decades are radical enzyme mechanisms, cell signaling cascades, antioxidant activities, and free radical-induced damage of biomolecules. In addition, identification of modified biomolecules opened the way for the evaluation of in vivo damage through biomarkers. When studying free radical-based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simpl… Show more

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2022

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Cited by 3 publications

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Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

et al. 2022

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The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried out a compositional evaluation of brain tissue for changes in parallel DNA and lipids compartments. DNA damage was measured by four purine 5′,8-cyclo-2′-deoxynucleosides, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), and 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA). In brain lipids, the twelve most representative fatty acid levels, which were mostly obtained from the transformation of glycerophospholipids, were followed up during the aging and disease progressions. The progressive DNA damage due to age and tumoral conditions was confirmed by raised levels of 5′S-cdG and 5′S-cdA. In the brain, the remodeling involved a diminution of palmitic acid accompanied by an increase in arachidonic acid, along both age and tumor progressions, causing increases in the unsaturation index, the peroxidation index, and total TFA as indicators of increased oxidative and free radical reactivity. Our results contribute to the ongoing debate on the central role of DNA and genome instability in the aging process, and on the need for a holistic vision, which implies choosing the best biomarkers for such monitoring. Furthermore, our data highlight brain tissue for its lipid remodeling response and inflammatory signaling, which seem to prevail over the effects of DNA damage.

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Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

et al. 2022

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Assessing the Formation of Purine Lesions in Mitochondrial DNA of Cockayne Syndrome Cells

et al. 2022

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Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in the mtDNA of wild type (wt) CSA (CS3BE–wtCSA) and wtCSB (CS1AN–wtCSB) cells and defective counterparts CS3BE and CS1AN in comparison with the corresponding total (t) DNA (t = n + mt). In particular, the four 5′,8–cyclopurine (cPu) and the two 8–oxo–purine (8–oxo–Pu) lesions were accurately quantified by LC–MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. The 8–oxo–Pu levels were found to be in the range of 25–50 lesions/107 nucleotides in both the mtDNA and tDNA. The four cPu were undetectable in the mtDNA both in defective cells and in the wt counterparts (CSA and CSB), contrary to their detection in tDNA, indicating a nonappearance of hydroxyl radical (HO•) reactivity within the mtDNA. In order to assess the HO• reactivity towards purine nucleobases in the two genetic materials, we performed γ–radiolysis experiments coupled with the 8–oxo–Pu and cPu quantifications on isolated mtDNA and tDNA from wtCSB cells. In the latter experiments, all six purine lesions were detected in both of the DNA, showing a higher resistance to HO• attack in the case of mtDNA compared with tDNA, likely due to their different DNA helical topology influencing the relative abundance of the lesions.

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

Chatgilialoglu

Grzelak

Skotnicki

et al. 2022

IJMS

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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.

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Biomimetic Radical Chemistry and Applications

Cited by 3 publications

References 43 publications

Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

Assessing the Formation of Purine Lesions in Mitochondrial DNA of Cockayne Syndrome Cells

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

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