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A Site-Specific Self-Assembled Light-up Rotor Probe for Selective Recognition and Stabilization of c-MYC G-Quadruplex DNA
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0002-7815-4494
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0001-7691-4392
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0001-6871-7663
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0001-6347-2169
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2020 (English)In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 12, no 24, p. 12950-12957Article in journal (Refereed) Published
Abstract [en]

Direct and unambiguous evidence of the formation of G-quadruplexes (G4s) in human cells have shown their implication in several key biological events and has emphasized their role as important targets for small-molecule cancer therapeutics. Here, we report on the first example of a self-assembled multitasking molecular-rotor G4-binder able to discriminate between an extensive panel of G4 and non-G4 structures and to selectively light-up (up to 105-fold), bind (nanomolar range), and stabilize the c-MYC promoter G4 DNA. In particular, association with the c-MYC G4 triggers the disassembly of its supramolecular state (disaggregation-induced emission, DIE) and induces geometrical restrictions (motion-induced change in emission, MICE) leading to a significant enhancement of its emission yield. Moreover, this optical reporter is able to selectively stabilize the c-MYC G4 and inhibit DNA synthesis. Finally, by using confocal laser-scanning microscopy (CLSM) we show the ability of this compound to localize primarily in the subnuclear G4-rich compartments of cancer cells. This work provides a benchmark for the future design and development of a new generation of smart sequence-selective supramolecular G4-binders that combine outstanding sensing and stability properties, to be utilized in anti-cancer therapy.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2020. Vol. 12, no 24, p. 12950-12957
National Category
Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Organic Chemistry Physical Chemistry
Research subject
Biochemistry; Organic Chemistry; Physical Chemistry; cell research
Identifiers
URN: urn:nbn:se:umu:diva-171513DOI: 10.1039/D0NR03404EISI: 000545599900025Scopus ID: 2-s2.0-85087110627OAI: oai:DiVA.org:umu-171513DiVA, id: diva2:1434557
Funder
Knut and Alice Wallenberg Foundation, KAW2015-0189Swedish Research Council, VR-NT 2017-05235Swedish Research Council, VR-MH 2018-02651The Kempe Foundations, SMK-1632Available from: 2020-06-03 Created: 2020-06-03 Last updated: 2023-03-24Bibliographically approved

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Deiana, MarcoChand, KaramJamroskovic, JanDas, Rabindra NathObi, IkennaChorell, ErikSabouri, Nasim

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Deiana, MarcoChand, KaramJamroskovic, JanDas, Rabindra NathObi, IkennaChorell, ErikSabouri, Nasim
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Department of Medical Biochemistry and BiophysicsDepartment of Chemistry
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Nanoscale
Biochemistry and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Organic ChemistryPhysical Chemistry

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