Publication 362

List   Previous   Next  
  1. Shybeka, I.; Maynard, J. R. J.; Saidjalolov, S.; Moreau, D.; Sakai, N.; Matile, S. “Dynamic Covalent Michael Acceptors to Penetrate Cells:  Thiol-Mediated Uptake with Tetrel-Centered Exchange Cascades, Assisted by Halogen-Bonding Switches” Angew. Chem. Int. Ed. 2022, 61, e202213433

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.

DOI: 10.1002/anie.202213433 

open archive unige:165965 • pdf