Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid

Sase, Shohei; Kakimoto, Ryo; Kimura, Ryutaro; Goto, Kei

doi:10.3390/molecules201219773

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…Furthermore, selenenic acids generated during the oxidation of selenols readily form diselenides by the reaction with unreacted selenols . Our and other groups have reported on the observation − and isolation − of nonselenocysteinyl-derivative selenenic acids by either kinetic or thermodynamic stabilization techniques. However, these nonselenocysteinyl derivatives do not adequately reproduce the characteristic reactivity of Sec–SeOH in proteins.…”

mentioning

confidence: 95%

Modeling the Catalytic Cycle of Glutathione Peroxidase by Nuclear Magnetic Resonance Spectroscopic Analysis of Selenocysteine Selenenic Acids

et al. 2021

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Although selenocysteine selenenic acids (Sec–SeOHs) have been recognized as key intermediates in the catalytic cycle of glutathione peroxidase (GPx), examples of the direct observation of Sec–SeOH in either protein or small-molecule systems have remained elusive so far, mostly due to their instability. Here, we report the first direct spectroscopic (1H and 77Se NMR) evidence for the formation of Sec–SeOH in small-molecule selenocysteine and selenopeptide model systems with a cradle-type protective group. The catalytic cycle of GPx was investigated using NMR-observable Sec–SeOH models. All the hitherto proposed chemical processes, i.e., not only those of the canonical catalytic cycle but also those involved in the bypass mechanism, including the intramolecular cyclization of Sec–SeOH to the corresponding five-membered ring selenenyl amide, were examined in a stepwise manner.

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confidence: 95%

Modeling the Catalytic Cycle of Glutathione Peroxidase by Nuclear Magnetic Resonance Spectroscopic Analysis of Selenocysteine Selenenic Acids

et al. 2021

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“…However, the steric demands of usual primary-alkyl groups are too small to protect such reactive species, and there has been no example of the synthesis of a thionitrate bearing a primary-alkyl group. Meanwhile, we have recently developed an effective primary-alkyl steric protection group, a BpqCH 2 group ( Figure 1 ), with a cavity-shaped framework and succeeded in the isolation of reactive species such as a sulfenic acid [ 18 ], a sulfenyl iodide [ 19 ], a selenenic acid [ 20 ], and a selenenyl iodide [ 21 ] by utilizing this substituent. Thus, a model study by utilizing the BpqCH 2 group was examined.…”

Section: Resultsmentioning

confidence: 99%

“…In the course of our studies on biologically relevant highly reactive species containing sulfur and selenium, we have developed various cavity-shaped substituents and demonstrated that these substituents are very effective for kinetic stabilization of highly reactive species that otherwise undergo facile bimolecular decomposition [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Herein, we report a model study on the bioactivation of an organic nitrate by a thiol, which is the fundamental chemical process in the thiol-dependent biotransformation of nitrates.…”

Section: Introductionmentioning

confidence: 99%

Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate

et al. 2016

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Thionitrates (R–SNO2) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used for the clinical treatment of angina pectoris for over 100 years. It has been proposed and widely accepted that a thiol would react with an organic nitrate to afford a thionitrate intermediate. However, there has been no example of an experimental demonstration of this elementary chemical process in organic systems. Herein, we report that aryl- and primary-alkyl-substituted thionitrates were successfully synthesized by the reaction of the corresponding lithium thiolates with organic nitrates by taking advantage of cavity-shaped substituents. The structure of a primary-alkyl-substituted thionitrate was unambiguously established by X-ray crystallographic analysis.

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“…The crystal structure of the truncated catalytic domain of mouse Dio3 has been solved [ 256 ], and it shows that the enzyme has a close structural similarity to atypical 2-Cys peroxiredoxins. The structure is compatible with Sec170 extracting the 5-iodine as a selenenyl-iodide, which should then hydrolyze to a selenenic acid intermediate, as supported by model studies with a synthetic alkylselenenyl-iodide [ 262 ]. It also shows that the thyronine ring is protonated via a network of conserved amino acids.…”

Section: Mammalian Selenoproteinsmentioning

confidence: 92%

Biological and Catalytic Properties of Selenoproteins

Chaudière

2023

IJMS

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Selenocysteine is a catalytic residue at the active site of all selenoenzymes in bacteria and mammals, and it is incorporated into the polypeptide backbone by a co-translational process that relies on the recoding of a UGA termination codon into a serine/selenocysteine codon. The best-characterized selenoproteins from mammalian species and bacteria are discussed with emphasis on their biological function and catalytic mechanisms. A total of 25 genes coding for selenoproteins have been identified in the genome of mammals. Unlike the selenoenzymes of anaerobic bacteria, most mammalian selenoenzymes work as antioxidants and as redox regulators of cell metabolism and functions. Selenoprotein P contains several selenocysteine residues and serves as a selenocysteine reservoir for other selenoproteins in mammals. Although extensively studied, glutathione peroxidases are incompletely understood in terms of local and time-dependent distribution, and regulatory functions. Selenoenzymes take advantage of the nucleophilic reactivity of the selenolate form of selenocysteine. It is used with peroxides and their by-products such as disulfides and sulfoxides, but also with iodine in iodinated phenolic substrates. This results in the formation of Se-X bonds (X = O, S, N, or I) from which a selenenylsulfide intermediate is invariably produced. The initial selenolate group is then recycled by thiol addition. In bacterial glycine reductase and D-proline reductase, an unusual catalytic rupture of selenium–carbon bonds is observed. The exchange of selenium for sulfur in selenoproteins, and information obtained from model reactions, suggest that a generic advantage of selenium compared with sulfur relies on faster kinetics and better reversibility of its oxidation reactions.

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Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid

Cited by 11 publications

References 25 publications

Modeling the Catalytic Cycle of Glutathione Peroxidase by Nuclear Magnetic Resonance Spectroscopic Analysis of Selenocysteine Selenenic Acids

Modeling the Catalytic Cycle of Glutathione Peroxidase by Nuclear Magnetic Resonance Spectroscopic Analysis of Selenocysteine Selenenic Acids

Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate

Biological and Catalytic Properties of Selenoproteins

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