Dynamic Covalent Michael Acceptors to Penetrate Cells: Thiol-Mediated Uptake with Tetrel-Centered Exchange Cascades, Assisted by Halogen-Bonding Switches

被引：5

作者：

Shybeka, Inga ^{[1
]}

Maynard, John R. J. ^{[1
]}

Saidjalolov, Saidbakhrom ^{[1
]}

Moreau, Dimitri ^{[1
]}

Sakai, Naomi ^{[1
]}

Matile, Stefan ^{[1
]}

机构：

[1] Univ Geneva, Natl Ctr Competence Res NCCR Chem Biol, Sch Chem & Biochem, Geneva, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 51期

基金：

瑞士国家科学基金会;

关键词：

Cellular Uptake; Dynamic Covalent Chemistry; Exchange Cascades; Reversible Michael Acceptors; Thiol-Mediated Uptake; FLUORESCENT-PROBE; CELLULAR UPTAKE; INHIBITORS; TRANSPORT; PROTEINS; DELIVERY; TENSION;

D O I：

10.1002/anie.202213433

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：6