Cell‐Penetrating Dynamic‐Covalent Benzopolysulfane Networks. (5th June 2019)

• Record Type: Journal Article
• Authors: Cheng, Yangyang; Zong, Lili; López‐Andarias, Javier; Bartolami, Eline; Okamoto, Yasunori; Ward, Thomas R.; Sakai, Naomi; Matile, Stefan
• Is Part Of: Angewandte Chemie. Volume 131:Number 28(2019)
• Page Start: 9622
• Page End: 9626
• Publication Date: 2019-06-05
• Subjects: Adaptive Netzwerke -- Cyclische Oligochalkogenide -- Dynamisch-kovalente Chemie -- Polysulfane -- Zellaufnahme; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201905003
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Benzopolysulfane werden als zellpenetrierende cyclische Oligochalkogenide eingeführt. Sie agieren über ein faszinierendes, in situ erzeugtes dynamisch‐kovalentes Netzwerk von Schwefelspezies, einschließlich Oligomeren mit bis zu 19 Schwefelatomen in einem Makrocyclus, die sehr hohe Reaktivität, Selektivität und Affinität zu Thiolen zeigen.