Thioredoxin reductase, an emerging target for anticancer metallodrugs. Enzyme inhibition by cytotoxic gold(iii) compounds studied with combined mass spectrometry and biochemical assays

MedChemComm ◽  
2011 ◽  
Vol 2 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Chiara Gabbiani ◽  
Guido Mastrobuoni ◽  
Francesca Sorrentino ◽  
Barbara Dani ◽  
Maria Pia Rigobello ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Enzyme Inhibition ◽  
Thioredoxin Reductase ◽  
Biochemical Assays ◽  
Anticancer Metallodrugs

Emerging Protein Targets for Anticancer Metallodrugs: Inhibition of Thioredoxin Reductase and Cathepsin B by Antitumor Ruthenium(II)−Arene Compounds

2008 ◽  
Vol 51 (21) ◽  
pp. 6773-6781 ◽  
Author(s):  
Angela Casini ◽  
Chiara Gabbiani ◽  
Francesca Sorrentino ◽  
Maria Pia Rigobello ◽  
Alberto Bindoli ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Thioredoxin Reductase ◽  
Protein Targets ◽  
Anticancer Metallodrugs

Biochemical Assays of Immobilized Oligonucleotides with Mass Spectrometry

Langmuir ◽  
2008 ◽  
Vol 24 (10) ◽  
pp. 5433-5438 ◽  
Author(s):  
Haim Tsubery ◽  
Milan Mrksich
Keyword(s):  
Mass Spectrometry ◽  
Biochemical Assays ◽  
Immobilized Oligonucleotides

Mass spectrometry-based biochemical assays for enzyme-inhibitor screening

2007 ◽  
Vol 26 (9) ◽  
pp. 867-883 ◽  
Author(s):  
Arjen R. de Boer ◽  
Henk Lingeman ◽  
Wilfried M.A. Niessen ◽  
Hubertus Irth
Keyword(s):  
Mass Spectrometry ◽  
Enzyme Inhibitor ◽  
Inhibitor Screening ◽  
Biochemical Assays

scholarly journals Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7600
Author(s):  
Iogann Tolbatov ◽  
Alessandro Marrone ◽  
Cecilia Coletti ◽  
Nazzareno Re
Keyword(s):  
Glutathione Peroxidase ◽  
Computational Chemistry ◽  
Thioredoxin Reductase ◽  
Organometallic Complexes ◽  
Correct Prediction ◽  
Computational Studies ◽  
Glutathione S Transferase ◽  
Protein Residues ◽  
Antitumor Compounds ◽  
Anticancer Metallodrugs

Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

scholarly journals Comparison of Liquid Chromatography/Mass Spectrometry, ELISA, and Phosphatase Assay for the Determination of Microcystins in Blue-Green Algae Products

2001 ◽  
Vol 84 (4) ◽  
pp. 1035-1044 ◽  
Author(s):  
James F Lawrence ◽  
Barbara Niedzwiadek ◽  
Cathie Menard ◽  
Benjamin P Y Lau ◽  
David Lewis ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Green Algae ◽  
Solid Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blue Green Algae ◽  
Biochemical Assays ◽  
Liquid Chromatography Tandem Mass ◽  
Protein Phosphatase Inhibition ◽  
Phosphatase Assay

Abstract More than 100 samples of blue-green algae products (consisting of Aphanizomenon, Spirulina, and unidentified blue-green algae) in the form of pills, capsules, and powders were collected from retail outlets from across Canada. The samples were extracted with 75% methanol in water and centrifuged to remove solids. Aliquots of the extracts along with spiked blank sample extracts were sent to each participating laboratory and independently analyzed for microcystins by enzyme-linked immunosorbent assay (ELISA), protein phosphatase inhibition assay, and by liquid chromatography–tandem mass spectrometry (LC–MS/MS) after sample cleanup using C18 solid–phase extraction. The results obtained by ELISA and LC–MS/MS agreed very well over a concentration range of about 0.5–35 μg/g. The colorimetric phosphatase results generally agreed with the other 2 methods. While the 2 biochemical assays measured total microcystin content compared with a standard of microcystin LR, the LC–MS/MS method measured specific microcystins (LA, LR, RR, YR) using external standards of these for identification and quantitation. Microcystin LR was found in all positive samples by LC–MS/MS. Microcystin LA was the only other microcystin found in the samples analyzed. These 2 microcystins represent essentially all the microcystins that were present in the extracts. Otherwise, the LC–MS/MS results would have been significantly lower than the results of the biochemical assays had other unknown microcystins been present.

scholarly journals Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability

2016 ◽  
Vol 113 (27) ◽  
pp. E3967-E3976 ◽  
Author(s):  
Keisuke Yoshida ◽  
Toru Hisabori
Keyword(s):  
Cooperative Control ◽  
Redox Regulation ◽  
Thioredoxin Reductase ◽  
Growth Conditions ◽  
Photosynthetic Performance ◽  
Redox Mediator ◽  
Regulation System ◽  
Biochemical Assays ◽  
Target Screening ◽  
Regulatory Functions

The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions.

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