ESI MS studies highlight the selective interaction of Auranofin with protein free thiols

2020 ◽  
Vol 49 (18) ◽  
pp. 5906-5913 ◽  
Author(s):  
Carlotta Zoppi ◽  
Luigi Messori ◽  
Alessandro Pratesi
Keyword(s):  
Mode Of Action ◽  
Cysteine Residues ◽  
Biologically Relevant ◽  
Esi Ms ◽  
Selective Interaction

The study of the mode-of-action of Auranofin, a cytotoxic gold(i) compound, reveals that it binds exclusively to the free and solvent-accessible cysteine residues of biologically relevant proteins.

scholarly journals Isolated domains of recombinant human apo-metallothionein 1A are folded at neutral pH: a denaturant and heat-induced unfolding study using ESI-MS

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Gordon W. Irvine ◽  
Natalie Korkola ◽  
Martin J. Stillman
Keyword(s):  
Critical Role ◽  
Cysteine Residues ◽  
Small Molecular Weight ◽  
Esi Ms ◽  
Neutral Ph ◽  
Induced Folding ◽  
Starting Point ◽  
High Metal ◽  
High Concentrations ◽  
Product Species

Metallothioneins (MTs) are characterized by their high metal loading capacity, small molecular weight, and abundant cysteine residues. It has long been thought that metal-free, or apo-MT peptides were unstructured and only adopted as a distinct conformation upon forming the metal clusters, described as metal-induced folding. More recent studies have suggested that the presence of a globular, yet loosely defined structure actually exists that can be disrupted or unfolded. Residue modification and ion-mobility ESI (IM-ESI)-MS have been used to examine this unusual unfolding process. The structure of apo-MT plays a critical role as the starting point in the flexible metalation pathways that can accommodate numerous soft metals. ESI-MS measurements of the product species formed following the cysteine alkylation of the isolated domain fragments of recombinant human apo-MT 1A with n-ethylmaleimide (NEM) were used in the present study to monitor the denaturant- and heat-induced unfolding at physiological pH. The results indicate that these apo-MT fragments adopt distinct structures at neutral pH that react co-operatively with NEM when folded and non-cooperatively when heated or exposed to high concentrations of the denaturant guanidinium chloride (GdmCl). From these studies, we can conclude that at neutral pH, the domain fragments are folded into globular structures where some of the free cysteine residues are buried within the core and are stabilized by hydrogen bonds. Metalation therefore, must take place from the folded conformation.

scholarly journals Thiol-Modification as Important Mode of Action for Allicin from Garlic (Allium sativum)

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 27 ◽  
Author(s):  
Martin C. H. Gruhlke
Keyword(s):  
Molecular Weight ◽  
Biological Activity ◽  
Active Compound ◽  
Mode Of Action ◽  
Allium Sativum ◽  
Cysteine Residues ◽  
Low Molecular Weight ◽  
Thiol Groups ◽  
Ancient Times ◽  
In Cells

Garlic is a common ingredient in food, normally used as spice but is also used since ancient times for its health beneficial activity. The thiosulfinate allicin is the first active compound in freshly damaged garlic tissue and reacts with thiol-groups. Hence, allicin is able to modify thiol groups, both of protein cysteine-residues and low-molecular weight thiols like glutathione. This thiol-modification is supposed to be an important mechanism for allicin’s biological activity. Here, the mechanisms and possible targets for allicin in cells are discussed.

β-Carboline directed regioselective hydroxylation by employing Cu(OAc)2 and mechanistic investigation by ESI-MS

2020 ◽  
Vol 18 (12) ◽  
pp. 2307-2311 ◽  
Author(s):  
Darshana Bora ◽  
Ramya Tokala ◽  
Stephy Elza John ◽  
Bitla Prasanth ◽  
Nagula Shankaraiah
Keyword(s):  
Biologically Relevant ◽  
Esi Ms ◽  
Mechanistic Investigation ◽  
Regioselective Hydroxylation ◽  
Biologically Relevant Molecules

This protocol demonstrates microwave-irradiated monohydroxylation on different heterocycles via C–H functionalization which leads into the development of biologically relevant molecules.

scholarly journals Electrospray Ionization Mass Spectrometry as a Valuable Tool in the Characterization of Novel Primaquine Peptidomimetic Derivatives

2009 ◽  
Vol 15 (5) ◽  
pp. 627-640 ◽  
Author(s):  
Nuno Vale ◽  
Joana Matos ◽  
Rui Moreira ◽  
Paula Gomes
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Ion Trap ◽  
Chemical Characterization ◽  
Ionization Mass ◽  
Biologically Relevant ◽  
Esi Ms ◽  
Physico Chemical ◽  
Fragmentation Patterns

Novel primaquine-derived antimalarials have been extensively characterized by electrospray ionization-ion trap mass spectrometry (ESI-MS). Experiments by in-source collision-induced dissociation (CID) in the nozzle–skimmer region (NSR) or by tandem mass spectrometry (MS/MS) are shown to be most valuable tools for the physico–chemical characterization of these 8-aminoquinolinic drugs that also bear the biologically relevant imidazolidin-4-one scaffold. It was possible to find parallelism between compound stability in the NSR and its reactivity towards hydrolysis at physiological pH and T. Moreover, MS/MS fragmentation patterns were characteristic for each family, providing a means for structural distinction of isomers and allowing interesting correlations to be found between the relative abundance of particular fragments and relevant structure–activity determinants, such as the Charton steric parameter, ν. In conclusion, this work provides a solid ground for establishing ESI-MS as a key tool for the physico–chemical characterization of biopharmaceuticals bearing the 8-aminoquinoline and/or the imidazolidin-4-one moieties.

Design, Synthesis and Insecticidal Activity of 3-(Ethylsulfonyl)-Pyridines Bearing Trifluoromethyl-Oxadiazole Fragment

2020 ◽  
Vol 17 ◽  
Author(s):  
Liangkun Zhong ◽  
Jing Yuan ◽  
Dan Pei ◽  
Xinghai Liu ◽  
Tianming Xu ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Insecticide Resistance ◽  
1H Nmr ◽  
13C Nmr ◽  
Insecticidal Activity ◽  
Mode Of Action ◽  
Pyridine Ring ◽  
Design Synthesis ◽  
Esi Ms ◽  
Mythimna Separate

Background: Oxadiazole fragment is one of the most prevalent structures in biochemicals, especially in the research of new pesticides. It is necessary to develop new insecticides with different mode of action for the treatment of insecticide resistance problems. And, it is worth exploring the new active insecticidal lead structures with oxadiazole fragments. Methods: We used a "splicing up" method introducing the trifluoromethyl-oxadiazole moiety to 3-(ethylsulfonyl)-pyridine structure, and replaced the 6-position on the pyridine ring by different substituted amines. Then, a series of novel 3- (ethylsulfonyl)-pyridines containing trifluoromethyl-oxadiazole moiety were designed and synthesized. All these title compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. Results and Discussion: The primary insecticidal activity results indicated that some of them (A1-A7, A10, A13-A14) exhibited good mortality against Mythimna separate at 500 mg/L (80-100%), and compounds A13 and A14 have moderate insecticidal activity against M. separate at 250 mg/L (50-55%). Discussion: The bioassay results showed that the designed compounds did not achieve excellent insecticidal activity by introducing the potential oxadiazole fragment. Therefore, it seems that the special physicochemical properties of the oxadiazole fragment should be considered in fragment splicing-based design. Conclusion: According to the bioassay studies, the results revealed that compounds A13 and A14 which may provide useful information for further design efficient insecticides.

Hetero-bimetallic cooperative catalysis for the synthesis of heteroarenes

2019 ◽  
Vol 17 (33) ◽  
pp. 7596-7631 ◽  
Author(s):  
Gaurav R. Gupta ◽  
Jagrut Shah ◽  
Kamlesh S. Vadagaonkar ◽  
Aditya G. Lavekar ◽  
Anant R. Kapdi
Keyword(s):  
Mode Of Action ◽  
Catalytic Systems ◽  
Biologically Relevant ◽  
Cooperative Catalysis

Review covering the synthesis of 5- and 6-membered as well as condensed heteroarenes, focussing on the combinations in cooperative catalytic systems in strategies used to achieve selectivity and also highlights the mode of action for the cooperative catalysis leading to the synthesis of commercially and biologically relevant heteroarenes.

scholarly journals Cytotoxicity of the Bacillus cereus Nhe Enterotoxin Requires Specific Binding Order of Its Three Exoprotein Components

2010 ◽  
Vol 78 (9) ◽  
pp. 3813-3821 ◽  
Author(s):  
Toril Lindbäck ◽  
Simon P. Hardy ◽  
Richard Dietrich ◽  
Marianne Sødring ◽  
Andrea Didier ◽  
...  
Keyword(s):  
Cell Surface ◽  
Bacillus Cereus ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Specific Binding ◽  
Vero Cells ◽  
Second Step ◽  
Cysteine Residues ◽  
Functional Roles ◽  
The Individual

ABSTRACT This study focuses on the interaction of the three components of the Bacillus cereus Nhe enterotoxin with particular emphasis on the functional roles of NheB and NheC. The results demonstrated that both NheB and NheC were able to bind to Vero cells directly while NheA lacked this ability. It was also shown that Nhe-induced cytotoxicity required a specific binding order of the individual components whereby the presence of NheC in the priming step as well as the presence of NheA in the final incubation step was mandatory. Priming of cells with NheB alone and addition of NheA plus NheC in the second step failed to induce toxic effects. Furthermore, in solution, excess NheC inhibited binding of NheB to Vero cells, whereas priming of cells with excess NheC resulted in full toxicity if unbound NheC was removed before addition of NheB. By using mutated NheC proteins where the two cysteine residues in the predicted β-tongue were replaced with glycine (NheCcys−) or where the entire hydrophobic stretch was deleted (NheChr−), the predicted hydrophobic β-tongue of NheC was found essential for binding to cell membranes but not for interaction with NheB in solution. All data presented here are compatible with the following model. The first step in the mode of action of Nhe is associated with binding of NheC and NheB to the cell surface and probably accompanied by conformational changes. These events allow subsequent binding of NheA, leading to cell lysis.

Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

1971 ◽  
Vol 29 ◽  
pp. 570-571
Author(s):  
E. A. Elfont ◽  
R. B. Tobin ◽  
D. G. Colton ◽  
M. A. Mehlman
Keyword(s):  
Chemical Composition ◽  
Rat Liver ◽  
Future Study ◽  
Mode Of Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Effective Inhibitor ◽  
Biochemical Effects ◽  
Glycerophosphate Dehydrogenase ◽  
Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

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