Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2019 Jun 7

PMID 31168906

Citations 18

Authors

Yangyang Cheng

Lili Zong

Javier Lopez-Andarias

Eline Bartolami

Yasunori Okamoto

Thomas R Ward

Naomi Sakai

Stefan Matile

Affiliations

Soon will be listed here.

Abstract

Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic-covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.

Citing Articles

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Synthesis of Seven Indolizine-Derived Pentathiepines: Strong Electronic Structure Response to Nitro Substitution in Position C-9.

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

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PMID: 36272154 PMC: 10098706. DOI: 10.1002/anie.202213433.

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