10236-58-5Relevant articles and documents
Kinetics of reaction of peroxynitrite with selenium- and sulfur-containing compounds: Absolute rate constants and assessment of biological significance
Storkey, Corin,Pattison, David I.,Ignasiak, Marta T.,Schiesser, Carl H.,Davies, Michael J.
, p. 1049 - 1056 (2015)
Peroxynitrite (the physiological mixture of ONOOH and its anion, ONOO-) is a powerful biologically-relevant oxidant capable of oxidizing and damaging a range of important targets including sulfides, thiols, lipids, proteins, carbohydrates and nucleic acids. Excessive production of peroxynitrite is associated with several human pathologies including cardiovascular disease, ischemic-reperfusion injury, circulatory shock, inflammation and neurodegeneration. This study demonstrates that low-molecular-mass selenols (RSeH), selenides (RSeR') and to a lesser extent diselenides (RSeSeR') react with peroxynitrite with high rate constants. Low molecular mass selenols react particularly rapidly with peroxynitrite, with second order rate constants k2 in the range 5.1×105-1.9×106 M-1 s-1, and 250-830 fold faster than the corresponding thiols (RSH) and many other endogenous biological targets. Reactions of peroxynitrite with selenides, including selenosugars are approximately 15-fold faster than their sulfur homologs with k2 approximately 2.5×103 M-1 s-1. The rate constants for diselenides and sulfides were slower with k2 0.72-1.3×103 M-1 s-1 and approximately 2.1×102 M-1 s-1 respectively. These studies demonstrate that both endogenous and exogenous selenium-containing compounds may modulate peroxynitrite-mediated damage at sites of acute and chronic inflammation, with this being of particular relevance at extracellular sites where the thiol pool is limited.
Selenazolidines as novel organoselenium delivery agents
Xie, Yang,Short, Megan D.,Cassidy, Pamela B.,Roberts, Jeanette C.
, p. 2911 - 2915 (2001)
Two new classes of selenazolidine-4(R)-carboxylic acids (2-oxo and 2-methyl-SCAs) were synthesized and characterized. Both were designed as latent forms of selenocysteine, intended to provide a chemically superior delivery form for selenium. The prodrugs may be clinically useful when selenium supplementation at supranutritional levels is indicated, such as in cancer chemoprevention.
Methyltransferase-directed derivatization of 5-hydroxymethylcytosine in DNA
Liutkeviaciute, Zita,Kriukiene, Edita,Grigaityte, Indre,Masevieius, Viktoras,Klimasauskas, Saulius
, p. 2090 - 2093 (2011)
Sequence-specific derivatization: Enzymatic methylation of cytosine in DNA is part of an epigenetic regulatory network in vertebrates. In the absence of the methylation cofactor S-adenosyl-L-methionine, bacterial cytosine-5 methyltransferases can catalyze the condensation of aliphatic thiols and selenols with 5-hydroxymethylcytosine, a recently discovered nucleobase in mammalian DNA, to yield 5-chalcogenomethyl derivatives (see scheme).
Selenomelanin: An Abiotic Selenium Analogue of Pheomelanin
Cao, Wei,McCallum, Naneki C.,Ni, Qing Zhe,Li, Weiyao,Boyce, Hannah,Mao, Haochuan,Zhou, Xuhao,Sun, Hao,Thompson, Matthew P.,Battistella, Claudia,Wasielewski, Michael R.,Dhinojwala, Ali,Shawkey, Matthew D.,Burkart, Michael D.,Wang, Zheng,Gianneschi, Nathan C.
, p. 12802 - 12810 (2020)
Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: Eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.
Generation of Recombinant Mammalian Selenoproteins through Genetic Code Expansion with Photocaged Selenocysteine
Abo, Masahiro,Chartier, Benjamin V.,Chatterjee, Abhishek,Chen, Jingjia,Edinger, Laura C.,Falco, Julia A.,Kelemen, Rachel E.,Peeler, Jennifer C.,Weerapana, Eranthie
, p. 1535 - 1540 (2020)
Selenoproteins contain the amino acid selenocysteine (Sec) and are found in all domains of life. The functions of many selenoproteins are poorly understood, partly due to difficulties in producing recombinant selenoproteins for cell-biological evaluation. Endogenous mammalian selenoproteins are produced through a noncanonical translation mechanism requiring suppression of the UGA stop codon and a Sec insertion sequence (SECIS) element in the 3′ untranslated region of the mRNA. Here, recombinant selenoproteins are generated in mammalian cells through genetic code expansion, circumventing the requirement for the SECIS element and selenium availability. An engineered orthogonal E. coli leucyl-tRNA synthetase/tRNA pair is used to incorporate a photocaged Sec (DMNB-Sec) at the UAG amber stop codon. DMNB-Sec is successfully incorporated into GFP and uncaged by irradiation of living cells. Furthermore, DMNB-Sec is used to generate the native selenoprotein methionine-R-sulfoxide reductase B1 (MsrB1). Importantly, MsrB1 is shown to be catalytically active after uncaging, constituting the first use of genetic code expansion to generate a functional selenoprotein in mammalian systems. The ability to site-specifically introduce Sec directly in mammalian cells, and temporally modulate selenoprotein activity, will aid in the characterization of mammalian selenoprotein function.
Studies on the reaction between reduced riboflavin and selenocystine
Dereven'kov, Ilia A.,Makarov, Sergei V.,Molodtsov, Pavel A.,Makarova, Anna S.
, p. 146 - 153 (2020/09/21)
Selenocysteine (Sec) is a crucial component of mammalian thioredoxin reductase (TrxR) where it serves as a nucleophile for disulfide bond rupture in thioredoxin (Trx). Generation of the reduced state of Sec in TrxR requires consecutive two electron transfer steps, namely: (i) from NADPH to flavin adenine dinucleotide, (ii) from reduced flavin to the disulfide bond Cys59-S-S-Cys64, and finally (iii) from Cys59 and Cys64 to the selenosulfide bond Cys497-S-Se-Sec498. In this work, we studied the reaction between reduced riboflavin (RibH2) and selenocystine (Sec-Sec), an oxidized form of Sec. The interaction between RibH2 and Sec-Sec proceeded relatively slowly in comparison with its reverse reaction, that is, reduction of riboflavin (Rib) by Sec. The rate constant for the reaction between RibH2 and Sec-Sec was (7.9?±?0.1)?×?10?2?M?1 s?1 (pH 7.0, 25.0°C). The reaction between Rib and Sec proceeded via two steps, namely, a rapid reversible binding of Rib to Sec having a protonated selenol group to form a Sec-Rib complex, followed by nucleophilic attack of Sec-Rib by a second Sec molecule harboring a deprotonated selenol group. The equilibrium constant for the overall reduction process of Rib by Sec is (1.2?±?0.1)?×?106?M?1 (25.0°C). The finding that the interaction of RibH2 with oxidized selenol is reversible with its equilibrium favored toward the reverse reaction provides an additional explanation for the exceptional mechanism of the mammalian Trx/TrxR system involving transient reduction of a disulfide bond.
