Extraction and Quantitation of Ketones and Aldehydes from Mammalian Cells Using Fluorous Tagging and Capillary LC-MS

Yuan, Wei; Li, Shuwei; Edwards, John A.

doi:10.1021/acs.analchem.5b01000

Cited by 24 publications

(15 citation statements)

References 24 publications

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“…Meanwhile, the aldehyde metabolites derived from the amine-containing pro-drugs are relatively stable, allowing us to analyze them by MS and also to extract them for probing the activity of TbALDH3 directly in the parasites. It actually reflects the general feature of the ketone and aldehyde metabolites in various biological and pathological contexts such as diabetes and alcoholism[ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

et al. 2018

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Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.

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Section: Discussionmentioning

confidence: 99%

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

et al. 2018

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“…As mentioned in Section 9, the LC–MS platform offers more analytical power for screening novel volatiles. Given the heavy reliance on the chemical derivatization of volatile components prior to instrument analysis, efforts to develop suitable chemical tags (Eggink et al., 2008; Yuan et al., 2015; Zheng et al., 2017) are needed for future LC–MS approaches. The precursor ion scan (MS/MS), stable isotope labeling (MS/MS), and isotopic pattern (HRMS) are operable modes for screening purpose.…”

Section: Analytical Trends In Embracing New Opportunitiesmentioning

confidence: 99%

Strategies for the identification and sensory evaluation of volatile constituents in wine

Chen

Darriet

2021

Comp Rev Food Sci Food Safe

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Wine aroma, which stems from complex perceptual and cognitive processes, is initially driven by a multitude of naturally occurring volatile constituents. Its interpretation depends on the characterization of relevant volatile constituents. With large numbers of volatile constituents already identified, the search for unknown volatiles in wine has become increasingly challenging. However, the opportunities to discover unknown volatile compounds contributing to the wine volatilome are still of great interest, as demonstrated by the recent identification of highly odorous trace (µg/L) to ultra-trace (ng/L) volatile compounds in wine. This review provides an overview of both existing strategies and future directions on identifying unknown volatile constituents in wine. Chemical identification, including sample extraction, fractionation, gas chromatography, olfactometry, and mass spectrometry, is comprehensively covered. In addition, this review also focuses on aspects related to sensory-guided wine selection, authentic reference standards, artifacts and interferences, and the evaluation of the sensory significance of discovered wine volatiles. Powerful key volatile odorants present at ultra-trace levels, for which these analytical approaches have been successfully applied, are discussed. Research areas where novel wine volatiles are likely to be identified are pointed out. The importance of perceptual interaction phenomena is emphasized. Finally, future avenues for the exploration of yet unknown wine volatiles by coupling analytical approaches and sensory evaluation are suggested.

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“…Different modification groups on the O-substituted hydroxylamine can achieve different detection purposes. For example, aminooxy-N-(3-perfluorooctyl-propyl) acetamide [98] is a fluorous O-substituted hydroxylamine tag and can selectively react with carbonyls to yield oximes, which can be extracted from the biological fluids using a fluorine spin column to simplify analysis. In addition, the fluorous O-substituted hydroxylamine tag can increase the hydrophobicity of the analytes, achieving a 30-fold increase in sensitivity.…”

Section: Hydroxylaminesmentioning

confidence: 99%

Progress and Challenges in Quantifying Carbonyl-Metabolomic Phenomes with LC-MS/MS

2021

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Carbonyl-containing metabolites widely exist in biological samples and have important physiological functions. Thus, accurate and sensitive quantitative analysis of carbonyl-containing metabolites is crucial to provide insight into metabolic pathways as well as disease mechanisms. Although reversed phase liquid chromatography electrospray ionization mass spectrometry (RPLC-ESI-MS) is widely used due to the powerful separation capability of RPLC and high specificity and sensitivity of MS, but it is often challenging to directly analyze carbonyl-containing metabolites using RPLC-ESI-MS due to the poor ionization efficiency of neutral carbonyl groups in ESI. Modification of carbonyl-containing metabolites by a chemical derivatization strategy can overcome the obstacle of sensitivity; however, it is insufficient to achieve accurate quantification due to instrument drift and matrix effects. The emergence of stable isotope-coded derivatization (ICD) provides a good solution to the problems encountered above. Thus, LC-MS methods that utilize ICD have been applied in metabolomics including quantitative targeted analysis and untargeted profiling analysis. In addition, ICD makes multiplex or multichannel submetabolome analysis possible, which not only reduces instrument running time but also avoids the variation of MS response. In this review, representative derivatization reagents and typical applications in absolute quantification and submetabolome profiling are discussed to highlight the superiority of the ICD strategy for detection of carbonyl-containing metabolites.

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Extraction and Quantitation of Ketones and Aldehydes from Mammalian Cells Using Fluorous Tagging and Capillary LC-MS

Cited by 24 publications

References 24 publications

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

Strategies for the identification and sensory evaluation of volatile constituents in wine

Progress and Challenges in Quantifying Carbonyl-Metabolomic Phenomes with LC-MS/MS

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