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Visible-Light-Switchable molecular glues for reversible control of protein function
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).ORCID iD: 0000-0002-3322-7864
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Key Laboratory of Organic Chemistry of Jiangxi Province, Jiangxi Science & Technology Normal University, Nanchang, China.
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2025 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 31, no 15, article id e202403808Article in journal (Refereed) Published
Abstract [en]

Chemically induced dimerization/proximity (CID/CIP) systems controlled by chemical dimerizers (also known as molecular glues) provide valuable means for understanding and manipulating complex, dynamic biological systems. In this study, we present the development of versatile chemo-optogenetic systems utilizing azobenzene-based photoswitchable molecular glues (sMGs) for reversible protein dimerization controlled by visible light. These systems allow multiple cycles of light-induced dimerization, overcoming the limitations of irreversible photolysis in previous systems. Through optimizing photoswitch properties and linker strategies, we achieved efficient and reversible control using blue, green, and red light. We demonstrate that these systems enable rapid and reversible control of protein function in vitro and in cells. The findings represent a significant advancement in chemo-optogenetics, offering opportunities to expand applications requiring precise spatiotemporal regulation of dynamic biological processes.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2025. Vol. 31, no 15, article id e202403808
Keywords [en]
Chemo-optogenetic system, CID, Molecular glue, Photoswitches, Visible light
National Category
Biochemistry Molecular Biology Physical Chemistry
Identifiers
URN: urn:nbn:se:umu:diva-234674DOI: 10.1002/chem.202403808ISI: 001401197700001PubMedID: 39805011Scopus ID: 2-s2.0-86000435179OAI: oai:DiVA.org:umu-234674DiVA, id: diva2:1934810
Funder
EU, European Research CouncilSwedish Research Council, 2018-04585Swedish Research Council, 2022-02932Knut and Alice Wallenberg FoundationGöran Gustafsson Foundation for Research in Natural Sciences and MedicineAvailable from: 2025-02-05 Created: 2025-02-05 Last updated: 2025-04-29Bibliographically approved

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Zhang, JunHerzog, Laura K.Li, ShuangChen, XiWu, Yao-Wen

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Zhang, JunHerzog, Laura K.Li, ShuangChen, XiWu, Yao-Wen
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Chemistry - A European Journal
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