Characterization of covalent protein modification by triclosan in vivo and in vitro via three-dimensional liquid chromatography-mass spectrometry: New insight into its adverse effects

Liu, Meixian; Li, Na; Zhang, Yida; Zheng, Zhiyuan; Zhuo, Yue; Sun, Baoqing; Bai, Liping; Zhang, Mingming; Chen, Guofang; Wu, Jian‐Lin

doi:10.1016/j.envint.2019.105423

Cited by 11 publications

(14 citation statements)

References 37 publications

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“…Some drugs have been reported to be metabolized to form small molecular derivatives by enzymes such as cytochrome P450 (CYPs) in microsomes [ 88 ]. Wu et al revealed an MS-based approach for the examination of three metabolized reactive products of triclosan, an antimicrobial agent, in rat liver microsome [ 89 ]. The rat microsome model was simulated as a living body that would metabolize assimilated drugs to specific derivatives, and these metabolites were identified using the MS system to provide information on the protein-modified portion for further target screening of triclosan.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Drug Targets of Broad-Spectrum Inhibitors with a Michael Acceptor Moiety Using Shotgun Proteomics

Chu

Sethy

Hsieh

et al. 2021

Viruses

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The Michael addition reaction is a spontaneous and quick chemical reaction that is widely applied in various fields. This reaction is performed by conjugating an addition of nucleophiles with α, β-unsaturated carbonyl compounds, resulting in the bond formation of C-N, C-S, C-O, and so on. In the development of molecular materials, the Michael addition is not only used to synthesize chemical compounds but is also involved in the mechanism of drug action. Several covalent drugs that bond via Michael addition are regarded as anticarcinogens and anti-inflammatory drugs. Although drug development is mainly focused on pharmaceutical drug discovery, target-based discovery can provide a different perspective for drug usage. However, considerable time and labor are required to define a molecular target through molecular biological experiments. In this review, we systematically examine the chemical structures of current FDA-approved antiviral drugs for potential Michael addition moieties with α, β-unsaturated carbonyl groups, which may exert an unidentified broad-spectrum inhibitory mechanism to target viral or host factors. We thus propose that profiling the targets of antiviral agents, such as Michael addition products, can be achieved by employing a high-throughput LC-MS approach to comprehensively analyze the interaction between drugs and targets, and the subsequent drug responses in the cellular environment to facilitate drug repurposing and/or identify potential adverse effects, with a particular emphasis on the pros and cons of this shotgun proteomic approach.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Drug Targets of Broad-Spectrum Inhibitors with a Michael Acceptor Moiety Using Shotgun Proteomics

Chu

Sethy

Hsieh

et al. 2021

Viruses

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“…RM-modified proteins. 90 It was found that the 3D SEC-SCX-RPLC platform produced a significant increase in the number of the modified proteins by 1400% (45 vs. 3), 36.4% (45 vs. 33), and 462.5% (45 vs. 8) compared to 1D RPLC, 2D SEC-RPLC, and SCX-RPLC platforms, respectively. Such increases in separation efficiency significantly improve the identification of modified proteins and benefit the DMPC analysis.…”

Section: Sample Separationmentioning

confidence: 95%

“…Organic reagents are commonly used because they do not need to be removed like detergents before MS analysis. For example, proteins are usually precipitated from complex biological solutions using a single reagent such as acetone, 29,90 or a mixture of organic reagents, such as methanol and chloroform (Table 2). 91 The precipitated protein is usually dissolved in urea, ammonium bicarbonate, or thiourea.…”

Section: Protein Extraction and Digestionmentioning

confidence: 99%

“…Individually, it is employed for 1D separation in proteomics analysis. 29,90 It is usually used for final dimensional chromatography in MD-LC strategies. In contrast, the retention on the HILIC column increases with increasing polarity or hydrophilicity of the peptide.…”

Section: Sample Separationmentioning

confidence: 99%

“…For example, the molecular compositions of three possible TCS modifications were input to the Mascot server as variable modifications, and 45 TCS-modified serum proteins were successfully identified. 90 Furthermore, the addition of C 8 H 7 NO 2 (NAPQI, RM of APAP) was input to the Mascot server as a variable modification of cysteine to directly identify NAPQI-modified peptides. 55 This generates an overview of the drug and its metabolitemodified target map.…”

Section: Data Analysis Strategiesmentioning

confidence: 99%

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Dual roles of drug or its metabolite−protein conjugate: Cutting‐edge strategy of drug discovery using shotgun proteomics

Gong

Chen

Sun

et al. 2022

Medicinal Research Reviews

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Many drugs can bind directly to proteins or be bioactivated by metabolizing enzymes to form reactive metabolites (RMs) that rapidly bind to proteins to form drug−protein conjugates or metabolite−protein conjugates (DMPCs). The close relationship between DMPCs and idiosyncratic adverse drug reactions (IADRs) has been recognized; drug discovery teams tend to avoid covalent interactions in drug discovery projects. Covalent interactions in DMPCs can provide high potency and long action duration and conquer the intractable targets, inspiring drug design, and development. This forms the dual role feature of DMPCs. Understanding the functional implications of DMPCs in IADR control and therapeutic applications requires precise identification of these conjugates from complex biological samples. While classical biochemical methods have contributed significantly to DMPC detection in the past decades, the low abundance and low coverage of DMPCs have become a bottleneck in this field. An emerging transformation toward shotgun proteomics is on the rise. The evolving shotgun proteomics techniques offer improved reproducibility, throughput, specificity, operability, and standardization. Here, we review recent progress in the systematic discovery of DMPCs using shotgun proteomics. Furthermore, the applications of shotgun proteomics supporting drug development, toxicity mechanism investigation, and drug repurposing processes are also reviewed and prospected.

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Technological development of multidimensional liquid chromatography-mass spectrometry in proteome research

Tai

Yang

et al. 2023

Journal of Chromatography A

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Characterization of covalent protein modification by triclosan in vivo and in vitro via three-dimensional liquid chromatography-mass spectrometry: New insight into its adverse effects

Cited by 11 publications

References 37 publications

Identification of Potential Drug Targets of Broad-Spectrum Inhibitors with a Michael Acceptor Moiety Using Shotgun Proteomics

Identification of Potential Drug Targets of Broad-Spectrum Inhibitors with a Michael Acceptor Moiety Using Shotgun Proteomics

Dual roles of drug or its metabolite−protein conjugate: Cutting‐edge strategy of drug discovery using shotgun proteomics

Technological development of multidimensional liquid chromatography-mass spectrometry in proteome research

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