ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cellular Biochemistry
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1629762
This article is part of the Research TopicMechanism Study of Bioactive Molecules Using Omics TechnologyView all 4 articles
Mollugin reacts with phenol thiol but not produce modification on cysteine discovered by a phenol thiol probe
Provisionally accepted
- Sun Yat-sen University, Guangzhou, China
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Electrophilic compounds from natural products (NPs) and metabolites can covalently modify the cysteines of target proteins to induce biological activities. To facilitate the discovery of novel NPs and metabolites, chemical probes with various thiol groups-mimicking the reactivity of cysteinehave been developed. These probes are designed to react with electrophilic groups of NPs and metabolites in an electrophilic addition mechanism, with the resulting adducts having molecular masses which equal to the sum of the probe and the target compound. This principle has been fundamental to analyzing mass spectrometry (MS) data and calculating the exact molecular weights of the target compound. In this study, we report a phenol thiol probe initially designed to mimic cysteine reacts with Mollugin and other structurally related NPs in an electrophilic free radical addition mechanism, and thus leads to the incorporation of not only the thiol probe but also a hydroxyl group in the adducts. Our results demonstrate that the phenol thiol group of the probe cannot always represent the thiol in cysteine to discover novel NPs or metabolites that can covalently modify cysteines.
Keywords: Nucleophilic chemical probe1, Mollugin2, Cysteine3, natural products4, Covalent modification5
Received: 16 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Liu, Qi, Feng, Li, Zhong and Bai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chuan Bai, Sun Yat-sen University, Guangzhou, China
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