期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 61, 期 51, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202213433
关键词
Cellular Uptake; Dynamic Covalent Chemistry; Exchange Cascades; Reversible Michael Acceptors; Thiol-Mediated Uptake
资金
- NMR
- MS
- ACCESS platform for services, and University of Geneva
- Swiss National Centre of Competence in Research (NCCR) Chemical Biology [51NF40-185898]
- NCCR Molecular Systems Engineering [51NF40-182895]
- Swiss NSF [200020, 204175]
- Swiss National Science Foundation (SNF) [200020_204175] Funding Source: Swiss National Science Foundation (SNF)
Chalcogen-centered cascade exchange chemistry plays a significant role in thiol-mediated uptake. Reversible Michael acceptors are found to both enable and inhibit thiol-mediated uptake, including the cytosolic delivery of proteins. These findings expand the understanding of thiol-mediated uptake and suggest the existence of a universal exchange network for matter entry into cells.
Chalcogen-centered cascade exchange chemistry is increasingly understood to account for thiol-mediated uptake, that is, the ability of reversibly thiol-reactive agents to penetrate cells. Here, reversible Michael acceptors are shown to enable and inhibit thiol-mediated uptake, including the cytosolic delivery of proteins. Dynamic cyano-cinnamate dimers rival the best chalcogen-centered inhibitors. Patterns generated in inhibition heatmaps reveal contributions from halogen-bonding switches that occur independent from the thyroid transporter MCT8. The uniqueness of these patterns supports that the entry of tetrel-centered exchangers into cells differs from chalcogen-centered systems. These results expand the chemical space of thiol-mediated uptake and support the existence of a universal exchange network to bring matter into cells, abiding to be decoded for drug delivery and drug discovery in the broadest sense.
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