Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry

Swaminathan, Kavya; Dyason, Jeffrey Clifford; Maggioni, Andrea; Itzstein, Mark von; Downard, Kevin M.

doi:10.1007/s00216-013-7068-x

Cited by 49 publications

(33 citation statements)

References 49 publications

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“…Some anthocyanins have been shown to decrease the infectivity of the influenza virus . In addition, the anthocyanin cyanidin‐3‐sambubioside, derived from black elderberry, as well as structurally related anthocyanins and catechins, could inhibit the function of influenza neuraminidase. Importantly, the molecular basis of this inhibition was found to be associated with the binding of the compounds within the so‐called 430‐cavity, adjacent to the active site, through a combination of mass spectrometry‐based experiments and computational molecular docking .…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the anthocyanin cyanidin‐3‐sambubioside, derived from black elderberry, as well as structurally related anthocyanins and catechins, could inhibit the function of influenza neuraminidase. Importantly, the molecular basis of this inhibition was found to be associated with the binding of the compounds within the so‐called 430‐cavity, adjacent to the active site, through a combination of mass spectrometry‐based experiments and computational molecular docking . This putative secondary sialic acid binding site forms part of an extended cavity not impacted by known resistance mutations in the active site that can render current antiviral therapeutics such as osteltamivir ineffective .…”

Section: Introductionmentioning

confidence: 99%

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Quantitation of anthocyanins in elderberry fruit extracts and nutraceutical formulations with paper spray ionization mass spectrometry

2017

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The ability to rapidly identify and quantitate, over a wide range of concentrations, anthocyanins in food and therapeutic products is important to ensuring their presence at medicinally significant levels. Sensitive, yet mild, analysis conditions are required given their susceptibility to degradation and transformation. Paper spray ionization has been used to detect and quantify the levels of anthocyanin levels in extracts of fresh and dried elderberries, and elderberry stems, as well as 3 commercially available nutraceutical formulations. The component cyanidin glucosides, including cyanidin-3-sambubioside, cyanidin-3-glucoside, cyanidin-3,5-diglucoside, cyanidin-3-sambubioside-5-glucoside, and the aglycone cyanidin, were readily detected in a range of sources. Quantitation was achieved by establishing a calibration plot from dilutions of a stock solution of cyanidin-3,5-diglucoside containing malvidin-3,5-diglucoside as an internal standard at a fixed concentration. The same standard was used to quantify the anthocyanin content in the fruit and nutraceutical formulations. Wide 5-fold variations in anthocyanin concentration were detected in the nutraceutical formulations from different suppliers ranging from 1050 to 5430 mg/100 g. These concentrations compared with 500 to 2370 mg/100 g measured in the dried stems and fruit, respectively. KEYWORDSanthocyanins, elderberry, paper spray mass spectrometry, quantitation Paper spray has been used to detect and quantitate pharmaceuticals in blood 26 and even for the direct analysis of biological tissues. 27 However, the range of compounds that can be successfully analysed by this relatively new ionization technique has yet to be fully explored. [28][29][30] This article reports on the first detection and quantitation of anthocyanins in elderberry fruit extracts and in elderberry-based nutraceutical formulations using PSI mass spectrometry (PSI-MS). | MATERIALS AND METHODS | Stock materials and solution preparationsStock solutions of cyanidin 3-sambubioside (CS) (Polyphenols, Sandnes, Norway) at 1 μg/μL and both cyanidin-3,5-diglucoside (CDG) and malvidin-3,5-diglucoside (Sigma-Aldrich, St. Louis, Missouri) at 100 ng/μL were prepared in methanol. To prepare calibration solutions, the cyanidin-3,5-diglucoside (CDG) stock solution (100 ng/μL) was diluted in methanol to final concentrations of 0.5, 1, 5, and 10 ng/μL. A volume (100 μL) of the stock malvidin diglucoside solution was added, as an internal standard, to an aliquot (900 μL) of each calibration solution.Three nutraceutical formulations (designated samples A, B, and C) reported to contain anthocyanins were purchased in capsule form from pharmacies. A portion (35 mg) of the capsule contents were dissolved in 70% ethanol (10 mL) containing 0.5% hydrochloric acid to maintain a low pH. To each solution, malvidin diglucoside stock solution was added to achieve a final concentration of 10 ng/μL as an internal standard.Black elderberry (Sambucus nigra) was obtained from an Australian grower (Ashbolt Farms, Plen...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitation of anthocyanins in elderberry fruit extracts and nutraceutical formulations with paper spray ionization mass spectrometry

2017

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“…After extraction and centrifugation, the reaction mixture is generally detected without separation by fluorimetry, 9,10 chemiluminescence, 11,12 UV spectrometry, 13 and mass spectrometry. [14][15][16] These in-solution screenings suffer from large sample consumption (at least microliters of each reactant), tedious sample processing and interference of optical detection.…”

Section: Screening Of Neuraminidase Inhibitors From Traditional Chinementioning

confidence: 99%

Screening of neuraminidase inhibitors from traditional Chinese medicine by transverse diffusion mediated capillary microanalysis

Zhao

Chen

2014

Biomicrofluidics

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A transverse diffusion mediated capillary microanalysis method has been developed for screening of neuraminidase inhibitors from traditional Chinese medicine. The enzyme, substrate and inhibitors were sequentially injected, mixed efficiently by transverse diffusion of laminar flow profiles, then incubated and separated in the same capillary. To enhance the mixing efficiency of reactants, running buffer was injected by alternately applying +5 kPa and -5 kPa at the capillary inlet and the procedure was repeated three times. The capillary electrophoresis (CE) separation conditions and reactants mixing conditions were optimized. Dual-wavelength detection was employed to eliminate the interference with natural compounds. The method has been applied to determine the kinetics constant of neuraminidase and screen 12 compounds from traditional Chinese medicine. Four compounds have been found to be positive for enzyme inhibition. The results are in good agreement with those reported in the literature. The method realized the mixing of substrate and enzyme with identical electrophoretic mobility. This novel CE method was simple, rapid, economic, and fully automated. Therefore, it was appropriate for neuraminidase inhibitors screening and could be extended to other high-throughput screening of active components from traditional Chinese medicine.

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“…Structure of a N1 neuraminidase monomer (PDB ID: 3NSS) in the region of the 430 and 150‐cavities showing the location of bound cyanidin and zanamivir. Reprinted from Swaminathan K et al () with permission [Springer].…”

Section: Application To Protein–drug/inhibitor Complexesmentioning

confidence: 99%

Indirect study of non‐covalent protein complexes by MALDI mass spectrometry: Origins, advantages, and applications of the “intensity‐fading” approach

Downard

2015

Mass Spectrometry Reviews

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This review article describes the origins, advantages, and application of an indirect approach with which to study protein and other macromolecular complexes and identify the nature and site of interaction interfaces by means of conventional matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). First reported in 1999, it involves the detection of ion depletion or the absence of ions associated with a binding partner or domain in the MALDI mass spectrum of a mixture of interacting components compared to that for an untreated control. Later referred to as intensity-fading in some applications, the method offers numerous advantages over the direct detection of protein and other macromolecule complexes by MALDI-MS and even electrospray ionization (ESI) MS. The origins of this indirect method, its development for use with gel-separated components, validation using companion biochemical assays, and application to a range of protein-antibody and protein-drug complexes are reviewed together with software specifically developed to aid with data interpretation. The sensitivity of the approach for revealing how subtle differences in the structure of the binding partners can be detected by MALDI-MS is also demonstrated. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:559-573, 2016.

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Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry

Cited by 49 publications

References 49 publications

Quantitation of anthocyanins in elderberry fruit extracts and nutraceutical formulations with paper spray ionization mass spectrometry

Quantitation of anthocyanins in elderberry fruit extracts and nutraceutical formulations with paper spray ionization mass spectrometry

Screening of neuraminidase inhibitors from traditional Chinese medicine by transverse diffusion mediated capillary microanalysis

Indirect study of non‐covalent protein complexes by MALDI mass spectrometry: Origins, advantages, and applications of the “intensity‐fading” approach

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