Fluorogenic In Situ Thioacetalization: Expanding the Chemical Space of Fluorescent Probes, Including Unorthodox, Bifurcated, and Mechanosensitive Chalcogen Bonds.

Autor:	Chen XX; Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland., Gomila RM; Departament de Química, Universitat de les Illes Balears, SP-07122 Palma de Mallorca, Spain., García-Arcos JM; Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland., Vonesch M; Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland., Gonzalez-Sanchis N; Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland., Roux A; Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland., Frontera A; Departament de Química, Universitat de les Illes Balears, SP-07122 Palma de Mallorca, Spain., Sakai N; Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland., Matile S; Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	JACS Au [JACS Au] 2023 Aug 21; Vol. 3 (9), pp. 2557-2565. Date of Electronic Publication: 2023 Aug 21 (Print Publication: 2023).
DOI:	10.1021/jacsau.3c00364
Abstrakt:	Progress with fluorescent flippers, small-molecule probes to image membrane tension in living systems, has been limited by the effort needed to synthesize the twisted push-pull mechanophore. Here, we move to a higher oxidation level to introduce a new design paradigm that allows the screening of flipper probes rapidly, at best in situ . Late-stage clicking of thioacetals and acetals allows simultaneous attachment of targeting units and interfacers and exploration of the critical chalcogen-bonding donor at the same time. Initial studies focus on plasma membrane targeting and develop the chemical space of acetals and thioacetals, from acyclic amino acids to cyclic 1,3-heterocycles covering dioxanes as well as dithiolanes, dithianes, and dithiepanes, derived also from classics in biology like cysteine, lipoic acid, asparagusic acid, DTT, and epidithiodiketopiperazines. From the functional point of view, the sensitivity of membrane tension imaging in living cells could be doubled, with lifetime differences in FLIM images increasing from 0.55 to 1.11 ns. From a theoretical point of view, the complexity of mechanically coupled chalcogen bonding is explored, revealing, among others, intriguing bifurcated chalcogen bonds. Competing Interests: The authors declare the following competing financial interest(s): The University of Geneva has licensed Flipper-TR probes to Spirochrome for commercialization. (© 2023 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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