74185-01-6Relevant articles and documents
Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif
Becker, Katja,Busker, Sander,Felber, Jan G.,Maier, Martin S.,Poczka, Lena,Scholzen, Karoline,Theisen, Ulrike,Thorn-Seshold, Julia,Thorn-Seshold, Oliver,Zeisel, Lukas,Arnér, Elias S. J.,Brandst?dter, Christina
supporting information, p. 8791 - 8803 (2021/06/27)
Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for redox enzymes and effector proteins (nM to μM concentrations), they must also be able to resist non-specific triggering by the ca. 50 mM background of non-catalytic cellular monothiols. However, no such selective reduction-sensing systems have yet been established. Here, we used rational structural design to independently vary thermodynamic and kinetic aspects of disulfide stability, creating a series of unusual disulfide reduction trigger units designed for stability to monothiols. We integrated the motifs into modular series of fluorogenic probes that release and activate an arbitrary chemical cargo upon reduction, and compared their performance to that of the literature-known disulfides. The probes were comprehensively screened for biological stability and selectivity against a range of redox effector proteins and enzymes. This design process delivered the first disulfide probes with excellent stability to monothiols yet high selectivity for the key redox-Active protein effector, thioredoxin. We anticipate that further applications of these novel disulfide triggers will deliver unique probes targeting cellular thioredoxins. We also anticipate that further tuning following this design paradigm will enable redox probes for other important dithiol-manifold redox proteins, that will be useful in revealing the hitherto hidden dynamics of endogenous cellular redox systems.
Oxidative Formation of Disulfide Bonds by a Chemiluminescent 1,2-Dioxetane under Mild Conditions
Sauer, Caroline S.,K?ckenberger, Johannes,Heinrich, Markus R.
, p. 9331 - 9338 (2020/08/14)
The oxidation of alkyl thiols to disulfides has been achieved under mild conditions using a chemiluminescent 1,2-dioxetane as a stoichiometric oxidant. Besides the mild and biocompatible reaction conditions, this approach offers the possibility to monitor the presence of thiols through oxidation and chemiluminescence of the remaining dioxetane.
Syntheses of prodrug-type phosphotriester oligonucleotides responsive to intracellular reducing environment for improvement of cell membrane permeability and nuclease resistance
Hayashi, Junsuke,Samezawa, Yusuke,Ochi, Yosuke,Wada, Shun-ichi,Urata, Hidehito
, p. 3135 - 3138 (2017/06/13)
We synthesized prodrug-type phosphotriester (PTE) oligonucleotides containing the six-membered cyclic disulfide moiety by using phosphoramidite chemistry. Prodrug-type oligonucleotides named “Reducing-Environment-Dependent Uncatalyzed Chemical Transforming (REDUCT) PTE oligonucleotides” were converted into natural oligonucleotides under cytosol-mimetic reductive condition. Furthermore, the REDUCT PTE oligonucleotides were robust to nuclease digestion and exhibited good cell membrane permeability.
Hydrogen Bonding-Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l-1,2-Diols with Chiral Nucleophilic Catalysts
Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
supporting information, p. 2778 - 2788 (2017/08/23)
An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min). (Figure presented.).
UV-Induced Disulfide Formation and Reduction for Dynamic Photopatterning
Li, Lei,Feng, Wenqian,Welle, Alexander,Levkin, Pavel A.
supporting information, p. 13765 - 13769 (2016/10/26)
UV-induced disulfide formation (UV-DF) and disulfide reduction (UV-DR) reactions for surface functionalization and dynamic photopatterning are presented. Both photochemical reactions allow for the spatially and temporally controlled, reversible transition
Tris(3-hydroxypropyl)phosphine (THPP): A mild, air-stable reagent for the rapid, reductive cleavage of small-molecule disulfides
McNulty, James,Krishnamoorthy, Venkatesan,Amoroso, Dino,Moser, Michael
supporting information, p. 4114 - 4117 (2015/11/03)
Tris(3-hydroxypropyl)phosphine (THPP) is demonstrated to be a versatile, water-soluble and air-stable reducing agent, allowing for the rapid, irreversible reductive cleavage of disulfide bonds in both aqueous and buffered aqueous-organic media. The reagent shows exceptional stability at biological pH under which condition it permits the rapid reduction of a wide range of differentially functionalized small-molecule disulfides.
A potent, versatile disulfide-reducing agent from aspartic acid
Lukesh III, John C.,Palte, Michael J.,Raines, Ronald T.
supporting information; experimental part, p. 4057 - 4059 (2012/04/10)
Dithiothreitol (DTT) is the standard reagent for reducing disulfide bonds between and within biological molecules. At neutral pH, however, >99% of DTT thiol groups are protonated and thus unreactive. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that can be synthesized from l-aspartic acid in a few high-yielding steps that are amenable to a large-scale process. DTBA has thiol pKa values that are ～1 unit lower than those of DTT and forms a disulfide with a similar E o′ value. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. The amino group of DTBA enables its isolation by cation-exchange and facilitates its conjugation. These attributes indicate that DTBA is a superior reagent for reducing disulfide bonds in aqueous solution.
Determination of dehydroascorbic acid in mouse tissues and plasma by using tris(2-carboxyethyl)phosphine hydrochloride as reductant in metaphosphoric acid/ethylenediaminetetraacetic acid solution
Sato, Yasunori,Uchiki, Takayuki,Iwama, Mizuki,Kishimoto, Yuki,Takahashi, Ryoya,Ishigami, Akihito
experimental part, p. 364 - 369 (2011/05/05)
Ascorbic acid (AA) has a strong anti-oxidant function evident as its ability to scavenge superoxide radicals in vitro. Moreover, AA is an essential ingredient for post-translational proline hydroxylation of collagen molecules. Dehydroascorbic acid (DHA), the oxidized form of AA, is generated from these reactions. In this study, we describe an improved method for assessing DHA in biological samples. The use of 35mM tris(2-carboxyethyl)-phosphine hydrochloride (TCEP) as a reductant completely reduced DHA to AA after 2 h on ice in a 5% solution of metaphosphoric acid containing 1mM ethylenediaminetetraacetic acid (EDTA) at pH 1.5. This method enabled us to measure the DHA content in multiple tissues and plasma of 6-weeks-old mice. The percentages of DHA per total AA differed markedly among these tissues, i.e., from 0.8 to 19.5%. The lung, heart, spleen and plasma had the highest levels at more than 10% of DHA per total AA content, whereas the cerebrum, cerebellum, liver, kidney and small intestine had less than 5% of DHA per total AA content. This difference in DHA content may indicate an important disparity of oxidative stress levels among physiologic sites. Therefore, this improved method provides a useful standard for all DHA determinations.
Method for distinguishing methicillin resistant S. aureus from methicillin sensitive S. aureus in a mixed culture
-
, (2008/06/13)
The present invention provides isolated oligonucleotides and methods for detecting a methicillin resistant Staphylococcus aureus in a sample, including a sample that comprises nucleic acid molecules of higher biological complexity than that of amplified nucleic acid molecules.
1,3-Dibromo-5,5-dimethylhydantoin [DBDMH] as an efficient and selective agent for the oxidation of thiols to Disulfides in solution or under solvent-free conditions
Khazaei, Ardeshir,Zolfigol, Mohammad Ali,Rostami, Amin
, p. 2959 - 2961 (2007/10/03)
A useful method for oxidation of various thiols to their corresponding disulfides with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) in very short reaction times and mild conditions under both solution and solvent-free conditions is described.
