23559-30-0

Usage

Uses

Used in Biochemistry and Pharmaceutical Industry:
N-ethylsuccinimido-S-glutathione is used as a protein modifier and stabilizer for its ability to create stable adducts with proteins, which can be used for various analytical and biological applications.
Used in Protein Research:
N-ethylsuccinimido-S-glutathione is used as a tool for studying protein structure and function, as it allows for the specific attachment of the compound to proteins, facilitating the investigation of their properties and interactions.
Used in Drug Development:
N-ethylsuccinimido-S-glutathione is used as a potential therapeutic agent for its antioxidant properties, which can protect proteins from oxidative damage, and its ability to modify and stabilize proteins, potentially leading to the development of new drugs and therapies.

InChI:InChI=1/C16H24N4O8S/c1-2-19-12(22)5-10(15(19)26)29-7-9(18)14(25)20(6-13(23)24)11(21)4-3-8(17)16(27)28/h8-10H,2-7,17-18H2,1H3,(H,23,24)(H,27,28)/t8-,9-,10?/m0/s1

Upstream product

• 128-53-0 N-Ethylmaleimide 
• 27025-41-8 Oxidized glutathione 
• 1336858-35-5 C₁₄H₁₅NO₄S 
• 70-18-8 GLUTATHIONE 

Relevant academic research and scientific papers

Extending the Scope of1H NMR-Based Blood Metabolomics for the Analysis of Labile Antioxidants: Reduced and Oxidized Glutathione

Glutathione is a ubiquitous cellular antioxidant, which is critically required to protect cells from oxidative damage and free radical injury. It is practically impossible to analyze glutathione in its native form after isolation from biological mixtures since the active form (reduced glutathione, GSH) spontaneously gets converted to the oxidized form (oxidized glutathione, GSSG). To address this challenge, numerous highly sensitive detection methods, including mass spectrometry, have been used in conjunction with derivatization to block the oxidation of GSH. Efforts so far to quantitate GSH and GSSG using the nuclear magnetic resonance (NMR) spectroscopy method have remained unsuccessful. With a focus on addressing this challenge, in this study, we describe an extension to our recent whole blood analysis method [Anal. Chem.2017, 89, 4620?4627] that includes the important antioxidants GSH and GSSG. Fresh and frozen human whole blood specimens as well as standard GSH and GSSG were comprehensively investigated using NMR without and with derivatization usingN-ethylmaleimide (NEM). NMR experiments detect two diastereomers, distinctly, for the derivatized GSH and enable the analysis of both GSH and GSSG in human whole blood with an accuracy of >99%. Interestingly, the excess (unreacted) NEM used for blocking the GSH can be removed from the samples during a drying step after extraction, with no need for additional processing. This is an important characteristic that offers an added advantage for simultaneous analysis of the antioxidants (GSH and GSSG), redox coenzymes (oxidized nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide (NADH), oxidized nicotinamide adenine dinucleotide phosphate (NADP+), reduced nicotinamide adenine dinucleotide phosphate (NADPH)), energy coenzymes (adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP), adenosine 5′-monophosphate (AMP)), and a large number of other blood metabolites using the same one-dimensional (1D) NMR spectrum. The presented method broadens the scope of global metabolite profiling and adds a new dimension to NMR-based blood metabolomics. Further, the method demonstrated here for human blood can be extended to virtually any biological specimen.

A highly sensitive luminescent probe based on Ru(II)-bipyridine complex for Cu2+, L-Histidine detection and cellular imaging

A ruthenium(II) bipyridyl complex conjugated with functionalized Schiff base (RuA) has been synthesized and functioned as a luminescent probe. The luminescence of RuA was greatly quenched by Cu2+ due to its molecular coordination with paramagnetic Cu2+. Subsequently, the addition of L-Histidine can turn on the luminescence of the RuA-Cu(II) ensemble, which can be attributed to the replacement of RuA in RuA-Cu(II) ensemble by L-Histidine. On the basis of the quenching and recovery of the luminescence of RuA, we proposed a rapid and highly sensitive on-off-on luminescent assay for sensing Cu2+ and L-Histidine in aqueous solution. Under the optimal conditions, Cu2+ and L-Histidine can be detected in the concentration range of 5 nM–9.0 μM and 50 nM–30 μM, respectively, and the corresponding detection limits were calculated to be 0.35 and 0.44 nM (S/N=3), separately. The proposed luminescent probe has been successfully utilized for the analysis of Cu2+ and L-Histidine in real samples (drinking water and biological fluids). Furthermore, the probe revealed good photostability, low cytotoxicity and excellent permeability, making it a suitable candidate for cell imaging and labeling in vitro.

Manipulation of Glutathione-Mediated Degradation of Thiol-Maleimide Conjugates

The retro Michael-type addition and thiol exchange of thioether succinimide click linkages in response to thiol-containing environments offers a novel strategy for the design of glutathione-sensitive degradable hydrogels for controlled drug delivery. Here we characterize the kinetics and extent of the retro Michael-type addition and thiol exchange with changes in both the pKa of the thiols and the identity of N-substituents of maleimides. A series of N-substituted thioether succinimides were prepared through typical Michael-type addition. Model studies (1H NMR, HPLC) of 4-mercaptophenylacetic acid (MPA, pKa 6.6) conjugated to N-ethyl maleimide (NEM), N-phenyl maleimide (NPM), or N-aminoethyl maleimide (NAEM) and then incubated with glutathione showed half-lives of conversion from 3.1 to 18 h, with extents of conversion from approximately 12% to 90%. The variations in the rates of exchange and hydrolytic ring opening appear to be mediated by resonance effects, electron-withdrawing capacity of the N-substituted moiety, as well as the potential for intramolecular catalytic hydrogen bonding of amine substituents with water (particularly in the case of ring opening). Further model studies of 4-mercaptohydrocinnamic acid (MPP, pKa 7.0) and N-acetyl-l-cysteine (NAC, pKa 9.5) conjugated to selected N-substituted maleimides and then incubated with glutathione showed half-lives of conversion from 3.6 to 258 h, with extents of conversion from approximately 1% to 90%. A higher pKa of the thiol decreased the rate of the exchange reaction and limited the impact of other electronic effects of N-substituents on the extents of conversion. Additional factors affecting the conversion kinetics were studied on NEM conjugates. The kinetics of the retro Michael-type addition and exchange reaction were not hindered by thiol traps of lower pKa, but were retarded in conditions of lower pH. These studies shed light into details of thiol and maleimide design that could be used to tune the rates of degradation of drug and polymer conjugates for a variety of applications.

An accurate mass spectrometric approach for the simultaneous comparison of GSH, Cys, and Hcy in L02 cells and HepG2 cells using new NPSP isotope probes

A novel accurate method was developed for simultaneous quantitative comparison of GSH, Cys and Hcy in normal cells and cancer cells using new NPSP isotope probes based on LC/ESI-MS.

Tunable degradation of maleimide-Thiol adducts in reducing environments

Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here, we show that the resulting succinimide thioether formed by the Michael-type addition of thiols to N-ethylm

Physiological activities of S-(1,2-dicarboxyethyl)glutathione as an intrinsic tripeptide present in liver, heart and lens

S-(1,2-Dicarboxyethyl)glutathione (DCE-GS, CAS 1115-52-2) found in rat liver, heart and lens in considerable amounts, showed an anti-inflammatory effect, which was evaluated by testing the inhibition of the experimental conjunctival edema of rats. An intravenous injection (3 mg/kg) prior to the carrageenan injection prevented the conjunctive edema formation by up to 30%. This peptide also inhibited the histamine release from rat mast cells induced by the compound 48/80. The peptide was added to the mast cells before addition of the compound 48/80 and an inhibition of the histamine release up to 96% at a 1 mmol/l concentration occurred. Furthermore, it displayed an antianaphylactic effect in rats using antibody against chicken egg albumin. An injection of the peptide (30 mg/kg) prior to the antigen administration inhibited color deposition up to 43%. Analogues or derivatives of DCE-GS were synthesized and tested for those inhibitory activities. However, there was no other peptide having stronger effects than DCE-GS and little structure-activity relationship among them.