Reactions of cysteine sulfenyl thiocyanate with thiols to give unsymmetrical disulfides

Nimmo, Susan L.; Lemma, Kelemu; Ashby, Michael T.

doi:10.1002/hc.20340

Cited by 15 publications

(4 citation statements)

References 30 publications

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“…HOSCN is a less potent oxidant compared to HOCl, and reacts by targeting free thiol (and selenol) residues with high selectivity [ [13] , [14] , [15] , [16] ]. This results in the formation of a range of reversible oxidation products, including sulfenyl thiocyanates, sulfenic acids and disulfides, which can potentially be repaired [ [17] , [18] , [19] , [20] ]. In addition, unlike HOCl, HOSCN can be detoxified by cellular antioxidant systems, particularly thioredoxin reductase (TrxR) [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

2020

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Myeloperoxidase (MPO) is a vital component of the innate immune system, which produces the potent oxidant hypochlorous acid (HOCl) to kill invading pathogens. However, an overproduction of HOCl during chronic inflammatory conditions causes damage to host cells, which promotes disease, including atherosclerosis. As such, there is increasing interest in the use of thiocyanate (SCN − ) therapeutically to decrease inflammatory disease, as SCN − is the favoured substrate for MPO, and a potent competitive inhibitor of HOCl formation. Use of SCN − by MPO forms hypothiocyanous acid (HOSCN), which can be less damaging to mammalian cells. In this study, we examined the ability of SCN − to modulate damage to macrophages induced by HOCl, which is relevant to lesion formation in atherosclerosis. Addition of SCN − prevented HOCl-mediated cell death, altered the extent and nature of thiol oxidation and the phosphorylation of mitogen activated protein kinases. These changes were dependent on the concentration of SCN − and were observed in some cases, at a sub-stoichiometric ratio of SCN − : HOCl. Co-treatment with SCN − also modulated HOCl-induced perturbations in the expression of various antioxidant and inflammatory genes. In general, the data reflect the conversion of HOCl to HOSCN, which can induce reversible modifications that are repairable by cells. However, our data also highlight the ability of HOSCN to increase pro-inflammatory gene expression and cytokine/chemokine release, which may be relevant to the use of SCN − therapeutically in atherosclerosis. Overall, this study provides further insight into the cellular pathways by which SCN − could exert protective effects on supplementation to decrease the development of chronic inflammatory diseases, such as atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

2020

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“…10 While the resultant disulfides are typically only stable in protic solvents under very acidic conditions, it appears that this reaction can take place within the active site of FabF, and that the local environment facilitates the formation of the FabF-AcpP disulfide bond. Since unlabeled holo -AcpP does not readily form a crosslink with FabF in vitro (Figure S11), we speculate that the cyanylation of AcpP either mimics a nascent substrate and induces a conformational change that alters the orientation of AcpP with respect to KS, 11 or facilitates crosslinking via an S N 2-type reaction by providing a robust leaving group.…”

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confidence: 99%

“…Reactions of cysteine sulfenyl thiocyanates with thiols are known to afford asymmetric disulfides . While the resultant disulfides are typically stable only in protic solvents under very acidic conditions, it appears that this reaction can take place in the active site of FabF and that the local environment facilitates the formation of the FabF–AcpP disulfide bond.…”

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confidence: 99%

Acyl Carrier Protein Cyanylation Delivers a Ketoacyl Synthase–Carrier Protein Cross-Link

et al. 2017

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Acyl carrier proteins (ACPs) are central hubs in polyketide and fatty acid biosynthetic pathways, but the fast motions of the ACP’s phosphopantetheine (Ppant) arm make its conformational dynamics difficult to capture using traditional spectroscopic approaches. Here we report that converting the terminal thiol of E. coli ACP’s Ppant arm into a thiocyanate activates this site to form a selective crosslink with the active site cysteine of its partner ketoacyl synthase (KS; FabF). The reaction releases a cyanide anion, which can be detected by infrared spectroscopy. This represents a practical and generalizable method to obtain and visualize ACP-protein complexes relevant to biocatalysis and will be valuable in future structural and engineering studies.

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“…HOSCN primarily targets both low-molecular mass and protein thiol (free Cys) residues. ,,,, This selective reactivity is quite different from HOCl and HOBr, which react rapidly with a wide range of biological substrates (reviewed in ref ). The initial products of the reaction of HOSCN with thiol groups are thiosulfenyl thiocyanate species (RS-SCN) (reaction ). ,, These derivatives are hydrolyzed to sulfenic acid (RSOH) intermediates (reaction ) or react with other thiol molecules to form disulfides (reaction ), though steric constraints may prevent this reaction in proteins. ,, Oxidized glutathione (GSSG) is the only product observed on treatment of isolated GSH with HOSCN, , though mixed Cys dimers have also been reported with other low-molecular mass thiol compounds under acidic conditions . Whether HOSCN plays a role in the glutathionylation of proteins, and subsequent regulation of various cellular signaling processes, has yet to be confirmed experimentally. normalR‐SH + HOSCN → normalRS‐SCN + normalH 2 normalO normalRS‐SCN + normalH 2 normalO → normalRS‐OH + SCN − + normalH + normalRS‐SCN + normalR 1 normal‐SH → normalRS‐S normalR 1 + SCN − + normalH + …”

Section: Formation Of Hoscn In Biological Systemsmentioning

confidence: 99%

Hypothiocyanous Acid: Benign or Deadly?

Barrett

Hawkins

2011

Chem. Res. Toxicol.

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Hypothiocyanous acid (HOSCN) is produced in biological systems by the peroxidase-catalyzed reaction of thiocyanate (SCN–) with H2O2. This oxidant plays an important role in the human immune system, owing to its potent bacteriostatic properties. Significant amounts of HOSCN are also formed by immune cells under inflammatory conditions, yet the reactivity of this oxidant with host tissue is poorly characterized. Traditionally, HOSCN has been viewed as a mild oxidant, which is innocuous to mammalian cells. Indeed, recent studies show that the presence of SCN– in airways has a protective function, by preventing the formation of other, more damaging, inflammatory oxidants. However, there is an increasing body of evidence that challenges this dogma, showing that the selectivity of HOSCN for specific thiol-containing cellular targets results in the initiation of significant cellular damage. This propensity to induce cellular dysfunction is gaining considerable interest, particularly in the cardiovascular field, as smokers have elevated plasma SCN–, the precursor for HOSCN. This review will outline the beneficial and detrimental aspects of HOSCN formation in biological systems.

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Reactions of cysteine sulfenyl thiocyanate with thiols to give unsymmetrical disulfides

Abstract: Cysteine sulfenyl thiocyanate (CSSCN) reacts with thiols at pH 0 to cleanly yield disulfides. 2-Mercaptoethanol

Cited by 15 publications

References 30 publications

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

Role of thiocyanate in the modulation of myeloperoxidase-derived oxidant induced damage to macrophages

Acyl Carrier Protein Cyanylation Delivers a Ketoacyl Synthase–Carrier Protein Cross-Link

Hypothiocyanous Acid: Benign or Deadly?

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