On the Reactions of Thiols, Sulfenic Acids, and Sulfinic Acids with Hydrogen Peroxide

Chauvin, Jean‐Philippe R.; Pratt, Derek A.

doi:10.1002/ange.201610402

Cited by 20 publications

(18 citation statements)

References 46 publications

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“…By contrast, our previous studies 5 and present data indicate a dynamic S -sulfenylome, with >60% undergoing substantial fold-changes during H 2 O 2 stress in A549 cells. Regarding the lineage between sulfenic and sulfinic acid states, our findings can be rationalized from several standpoints: From a chemical perspective, the reaction between a thiolate and H 2 O 2 is more facile, compared to the less nucleophilic sulfur atom in sulfinic acid and this difference in rates constants has been well documented 2,41 . From a biological viewpoint, S -sulfinylation may accumulate due to the moderate intrinsic catalytic activity of SRX 11,15 and the observation that not all protein sulfinic acids appear to be viable substrates for SRX-targeted reduction.…”

Section: Discussionmentioning

confidence: 55%

“…5a ). The finding that S -sulfenylation is considerably more dynamic is supported by mechanistic studies 41 which indicate that oxidation of a thiolate to sulfenic acid is more facile than oxidation of sulfenic to sulfinic acid (reflecting the intrinsic reduction in sulfur nucleophilicity) and cell-based studies that highlight the ability of antioxidant systems to protect cysteines from hyperoxidation 7,13,15,35 .…”

Section: Resultsmentioning

confidence: 95%

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Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Fu²,

et al. 2018

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Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.

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Section: Discussionmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 95%

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Fu²,

et al. 2018

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“…This approach was previously used to monitor the thiol oxidation reaction by 19 F NMR. 10 Additionally, 9-fluorotriptycene-10-sulfenic acid ( 7O ) is a stable sulfenic acid, which has been previously isolated and characterized. 10 Therefore, 9-fluorotriptycene-10-thiol ( 7 ) and the sulfenic acid 7O were synthesized by using similar procedures reported in the literature.…”

Section: Resultsmentioning

confidence: 99%

Photo-oxidation and Thermal Oxidations of Triptycene Thiols by Aryl Chalcogen Oxides

et al. 2020

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Oxidation of thiols yield sulfenic acids, which are very unstable intermediates. As sulfenic acids are reactive, they form disulfides in the presence of thiols. However, sulfenic acids also oxidize to sulfinic acids (−SO 2 H) and sulfonic acids (−SO 3 H) at higher concentrations of oxidants. Hydrogen peroxide is a commonly used oxidant for the oxidation of thiols to yield sulfenic acids. However, hydrogen peroxide also oxidizes other reactive functional groups present in a molecule. In this work, the reaction intermediates arising from the oxidation of sterically hindered thiols by aryl chalcogen oxides, dibenzothiophene S -oxide (DBTO), dibenzoselenophene Se -oxide (DBSeO), and dibenzotellurophene Te -oxide (DBTeO), were investigated. Photodeoxygenation of DBTO produces triplet atomic oxygen [O( 3 P)], which has previously shown to preferentially react with thiols over other functional groups. Similarly, aryl selenoxides have also shown that they can thermally react selectively with thiols at room temperature to yield disulfides. Conversely, aryl telluroxides have been reported to oxidize thiols to disulfides thermally with no selectivity toward thiols. The results from this study demonstrate that sulfenic acids are an intermediate in the oxidation of thiols by DBTeO and by photodeoxygenation of DBTO. The results also showed that the oxidation of thiols by DBSeO yields sulfonic acids. Triptycene-9-thiol and 9-fluorotriptycene-10-thiol were for the thiols used in this oxidation reaction. This work expands the list of oxidants that can be used to oxidize thiols to obtain sulfenic acids.

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“…However, in an environment of chronic ONS, increasing hydrogen peroxide levels have pathogenic consequences, not least by inducing over-oxidation of crucial functional cysteine groups in the thioredoxin [ 58 , 303 ] and glutathione systems, potentially rendering both systems inactive [ 304 ]. It should be noted that such inactivation may be reversible if caused by oxidation of thiolate anions to sulfenic acid but the weight of evidence suggests that the oxidation of the latter to sulfonic acid is not [ 305 ]. This essentially permanent disruption of redox-based cellular signalling may be one factor explaining the relatively disappointing responses achieved by anti-oxidant therapy in neurodegenerative and neuroprogressive illnesses.…”

Section: Loss Of Cellular Redox Homeostasismentioning

confidence: 99%

Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

Morris

Puri²,

Olive

et al. 2020

BMC Med

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Background Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. Main text Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. Conclusions Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.

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On the Reactions of Thiols, Sulfenic Acids, and Sulfinic Acids with Hydrogen Peroxide

Abstract: The reaction of thiols with H 2

Cited by 20 publications

References 46 publications

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Photo-oxidation and Thermal Oxidations of Triptycene Thiols by Aryl Chalcogen Oxides

Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

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