The Chemistry of Selenocysteine

Metanis, Norman; Beld, Joris; Hilvert, Donald

doi:10.1002/9780470682531.pat0582

Cited by 17 publications

(21 citation statements)

References 453 publications

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“…Selenium and sulphur belong to the same main group of elements; therefore, 21st proteinogenic amino selenocysteine and Cys residue exhibit rather similar properties in terms of reactivity for bioconjugation. [792][793][794] For instance, both Hilvert's 738 and Raines's group 736 demonstrated that C-terminal peptide thioesters react smoothly with peptide fragments containing a N-terminal selenocysteine in exactly the same manner as with corresponding cysteine analogues. Presumably proceeding through the same mechanism as NCL (Section 2.3.1), the first step of the ligation process consists in the nucleophilic attack on the thioester by selenolate to give a selenoester intermediate that subsequently rearranges to give a native chemical bond.…”

Section: Selenocysteinementioning

confidence: 99%

Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation

2015

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Bioconjugation methodologies have proven to play a central enabling role in the recent development of biotherapeutics and chemical biology approaches. Recent endeavours in these fields shed light on unprecedented chemical challenges to attain bioselectivity, biocompatibility, and biostability required by modern applications. In this review the current developments in various techniques of selective bond forming reactions of proteins and peptides were highlighted. The utility of each endogenous amino acid-selective conjugation methodology in the fields of biology and protein science has been surveyed with emphasis on the most relevant among reported transformations; selectivity and practical use have been discussed.

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Section: Selenocysteinementioning

confidence: 99%

Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation

2015

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“…Here we describe a macrocyclization strategy that exploits the advantageous physicochemical properties of selenocysteine (Sec, U) instead of cysteine to accomplish effective crosslinking that can be applied not only to native OT but also to a wide range of other peptide sequences. In recent years, Sec has been incorporated into several bioactive peptides with innovative properties 23,24 . For example, substitution of S-S bonds by isosteric Se-Se bonds can improve peptide folding and stability [25][26][27] .…”

Section: Resultsmentioning

confidence: 99%

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

et al. 2014

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Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general.

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“…Selenium is a trace element in humans, found primarily in the form of the amino acids selenocysteine (SeCys) and selenomethionine (SeMet) [1][2][3][4]. Selenocysteine is present at the active site of several redox enzymes, such as thioredoxin reductases, and can react with its sulfur analogue cysteine to form a selenylsulfide bond during the reduction of disulfides [5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Voltammetric behavior of selenocystine at modified gold substrates

Walker

Karnaukh

Dewan

et al. 2016

Electrochemistry Communications

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The voltammetric response of seleno-L-cystine has been studied at gold substrates under physiological conditions. The reactivity of diselenides is utilized to generate a modified electrode surface, which in turn allows for electroanalysis of solution-based selenium species. Stable and reproducible voltammetry is observed for selenocystine reduction at pH 7 on selenium-modified gold substrates (E mid =-486 mV vs. Ag/AgCl) and is consistent with a diffusionally controlled process. Modification of the gold surface is readily achieved via electrochemical cycling in the presence of a diselenide source at conventional scan rates. These studies afford voltammetric characterization of the selenocystine / selenocysteine redox couple under physiologically relevant conditions and highlight the potential utility of selenium-modified substrates for electroanalysis of chalcogen-containing species.

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The Chemistry of Selenocysteine

Cited by 17 publications

References 453 publications

Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation

Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation

Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

Voltammetric behavior of selenocystine at modified gold substrates

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