“…(545) Although the precise reasons for incorporation of Sec into proteins is debated,(546,547) it is clear that Sec is intrinsically more nucleophilic than cysteine. (548) Unsurprisingly, Sec is a target of both ROS and RES. Glutathione peroxidase, a selenoprotein, was shown to be oxidized at selenium to form a selenylamide that can be reactivated by addition of glutathione.…”
Section: Physicochemical Properties Of Biological Res and Ros And mentioning
The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation, (2) physicochemical properties, (3) mechanisms of action, (4) methods of interrogation, and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.
“…(545) Although the precise reasons for incorporation of Sec into proteins is debated,(546,547) it is clear that Sec is intrinsically more nucleophilic than cysteine. (548) Unsurprisingly, Sec is a target of both ROS and RES. Glutathione peroxidase, a selenoprotein, was shown to be oxidized at selenium to form a selenylamide that can be reactivated by addition of glutathione.…”
Section: Physicochemical Properties Of Biological Res and Ros And mentioning
The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation, (2) physicochemical properties, (3) mechanisms of action, (4) methods of interrogation, and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.
“…A suspension of RLi was prepared from 1,3-dimethoxybenzene (6.0 cm 3 , 46 mmol), a 15% hexane solution of n-butyllithium (26 cm 3 , 42 mmol), and a catalytic amount of N,N,NЈ,NЈtetramethylethylenediamine (TMEDA) (0.15 cm 3 ) under argon. 1 To this was added dropwise a solution of TeCl 4 (2.70 g, 10 mmol) dissolved in dry diethyl ether (30 cm 3 ), and the reaction mixture stirred at room temperature for 5 h to give a yellow suspension. Methanol (2 cm 3 ) was added with vigorous stirring, and the suspension filtered to give a white solid.…”
Section: Preparationsmentioning
confidence: 99%
“…As a part of our systematic investigation on the chemistry of such derivatives of a variety of elements, 1-5 we have recently reported the preparations and some basic properties of 2,6-dimethoxyphenyl derivatives of Group 16 elements, such as R 2 E and their oxides [E = S, Se or Te]. 1 We report here the preparations and properties of tris(2,6dimethoxyphenyl)telluronium salts, [R 3 Te]X, and bis(2,6-dimethoxyphenyl)tellurium dihalides, R 2 TeX 2 (see Scheme 1), together with the crystal structures and the temperaturedependent 1 H NMR spectra of R 2 TeX 2 .…”
“…Selenols are present in proteins that include Sec in their primary structure (i.e., selenoproteins) [86], differing from cysteine in the identity of the nucleophilic atom (selenium instead of sulfur). Compared to thiols, selenols are not only more acidic (Sec pK a =5.24 [87]) but also have much greater intrinsic nucleophilicity [88]. By contrast, acidity can limit thiol reactivity [76].…”
Section: Redox Biochemistry Of Scn− and Hoscnmentioning
Thiocyanate (SCN−) is an ubiquitous molecule in mammalian biology, reaching up to mM concentrations in extracellular fluids. Two-electron oxidation of SCN− by H2O2 produces hypothiocyanous acid (HOSCN), a potent antimicrobial species. This reaction is catalyzed by chordate peroxidases (e.g., myeloperoxidase and lactoperoxidase), occurring in human secretory mucosa, including the oral cavity, airway and alimentary tract, and regulates resident and transient flora as part of innate immunity. Increasing SCN− levels limits the concentrations of a family of 2-electron oxidants (H2O2, hypohalous acids and haloamines) in favor of HOSCN formation, altering the oxidative impact on host tissue by substitution of repairable thiol and selenol oxidations instead of biomolecule degradation. This fine-tuning of inflammatory oxidation paradoxically associates with maintained host defense and decreased host injury during infections, due in part to phylogenetic differences in the thioredoxin reductase system between mammals and their pathogens. These differences could be exploited by pharmacologic use of SCN−. Recent preclinical studies have identified antimicrobial and anti-inflammatory effects of SCN− in pulmonary and cardiovascular animal models, with implications for treatment of infectious lung disease and atherogenesis. Further research is merited to expand on these findings and identify other diseases where SCN− may be of use. High oral bioavailability and an increased knowledge of the biochemical effects of SCN− on a subset of pro-inflammatory reactions suggest clinical utility.
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