10236-58-5Relevant academic research and scientific papers
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.
Detection of Intracellular Selenol-Containing Molecules Using a Fluorescent Probe with Near-Zero Background Signal
Sun, Qi,Yang, Shu-Hou,Wu, Lei,Dong, Qing-Jian,Yang, Wen-Chao,Yang, Guang-Fu
, p. 6084 - 6091 (2016)
Selenocysteine (Sec), encoded as the 21st amino acid, is the predominant chemical form of selenium that is closely related to various human diseases. Thus, it is of high importance to identify novel probes for sensitive and selective recognition of Sec and Sec-containing proteins. Although a few probes have been reported to detect artificially introduced selenols in cells or tissues, none of them has been shown to be sensitive enough to detect endogenous selenols. We report the characterization and application of a new fluorogenic molecular probe for the detection of intracellular selenols. This probe exhibits near-zero background fluorescence but produces remarkable fluorescence enhancement upon reacting with selenols in a fast chemical reaction. It is highly specific and sensitive for intracellular selenium-containing molecules such as Sec and selenoproteins. When combined with flow cytometry, this probe is able to detect endogenous selenols in various human cancer cells. It is also able to image endogenous selenol-containing molecules in zebrafish under a fluorescence microscope. These results demonstrate that this molecular probe can function as a useful molecular tool for intracellular selenol sensing, which is valuable in the clinical diagnosis for human diseases associated with Sec-deficiency or overdose.
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.
A Photochemically Generated Selenyl Free Radical Observed by High Energy Resolution Fluorescence Detected X-ray Absorption Spectroscopy
Nehzati, Susan,Dolgova, Natalia V.,Sokaras, Dimosthenis,Kroll, Thomas,Cotelesage, Julien J. H.,Pickering, Ingrid J.,George, Graham N.
, p. 10867 - 10872 (2018)
Selenium-based selenyl free radicals are chemical entities that may be involved in a range of biochemical processes. We report the first X-ray spectroscopic observation of a selenyl radical species generated photochemically by X-ray irradiation of low-temperature solutions of l-selenocysteine. We have employed high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) and electron paramagnetic resonance (EPR) spectroscopy, coupled with density functional theory calculations, to characterize and understand the species. The HERFD-XAS spectrum of the selenyl radical is distinguished by a uniquely low-energy transition with a peak energy at 12659.0 eV, which corresponds to a 1s → 4p transition to the singly occupied molecular orbital of the free radical. The EPR spectrum shows the broad features and highly anisotropic g-values that are expected for a selenium free radical species. The availability of spectroscopic probes for selenyl radicals may assist in understanding why life chooses selenium over sulfur in selected biochemical processes.
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).
X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers
Pentelute, Brad L.,Gates, Zachary P.,Tereshko, Valentina,Dashnau, Jennifer L.,Vanderkooi, Jane M.,Kossiakoff, Anthony A.,Kent, Stephen B. H.
, p. 9695 - 9701 (2008)
Chemical protein synthesis and racemic protein crystallization were used to determine the X-ray structure of the snow flea antifreeze protein (sfAFP). Crystal formation from a racemic solution containing equal amounts of the chemically synthesized proteins D-sfAFP and L-sfAFP occurred much more readily than for L-sfAFP alone. More facile crystal formation also occurred from a quasi-racemic mixture of D-sfAFP and L-Se-sfAFP, a chemical protein analogue that contains an additional -SeCH2- moiety at one residue and thus differs slightly from the true enantiomer. Multiple wavelength anomalous dispersion (MAD) phasing from quasi-racemate crystals was then used to determine the X-ray structure of the sfAFP protein molecule. The resulting model was used to solve by molecular replacement the X-ray structure of L-sfAFP to a resolution of 0.98 A. The L-sfAFP molecule is made up of six antiparallel left-handed PPII helixes, stacked in two sets of three, to form a compact brick-like structure with one hydrophilic face and one hydrophobic face. This is a novel experimental protein structure and closely resembles a structural model proposed for sfAFP. These results illustrate the utility of total chemical synthesis combined with racemic crystallization and X-ray crystallography for determining the unknown structure of a protein.
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.
Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium Compounds
Mondal, Santanu,Mugesh, Govindasamy
, p. 1773 - 1780 (2019)
Halogenated nucleosides, such as 5-iodo-2′-deoxyuridine and 5-iodo-2′-deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single-strand breaks and intra- or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl-based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine-based nucleosides, such as 5-X-2′-deoxyuridine and 5-X-2′-deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo-cytidines was found to be faster than that of iodo-uridines. The initial rates of the deiodinations of 5-iodocytosine and 5-iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen-bond-mediated and addition/elimination pathway, respectively.
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.
Ribosomal synthesis of dehydroalanine-containing peptides
Seebeck, Florian P.,Szostak, Jack W.
, p. 7150 - 7151 (2006)
Dehydroalanine is a nonproteinogenic amino acid, but it is a component of a wide variety of natural products with therapeutic activities. Indeed, this α,β-unsaturated residue is a highly versatile building block due to its rigidifying effect on peptide backbones and its electrophilicity which allows site-specific thiol ligations of peptides with small molecules or proteins. To harness such versatility in genetically encoded, combinatorial peptide libraries, we report a simple and robust method for the ribosomal synthesis of dehydroalanine-containing peptides. Selenalysine, a selenium-containing lysine analogue, was recruited as a masked dehydroalanine equivalent. This residue is efficiently incorporated by a reconstituted Escherichia coli translation system at high fidelity and efficiency despite the presence of low levels of lysine. Mild oxidative conditions were used to convert selenalysine into dehydroalanine post-translationally. Using this method, we demonstrate the preparation of polyunsaturated and highly decorated peptides. This report is an important step toward the preparation and selection of large libraries of protein-reactive compounds with potential use as novel drugs or as analytical tools. Copyright
