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Sengupta, P., Jamroskovic, J. & Sabouri, N. (2023). A beginner's handbook to identify and characterize i-motif DNA. In: Hans Renata (Ed.), Methods in enzymology: . Elsevier
Öppna denna publikation i ny flik eller fönster >>A beginner's handbook to identify and characterize i-motif DNA
2023 (Engelska)Ingår i: Methods in enzymology / [ed] Hans Renata, Elsevier, 2023Kapitel i bok, del av antologi (Refereegranskat)
Abstract [en]

Genomic DNA exhibits an innate ability to manifest diverse sequence-dependent secondary structures, serving crucial functions in gene regulation and cellular equilibrium. While extensive research has confirmed the formation of G-quadruplex structures by guanine-rich sequences in vitro and in cells, recent investigations have turned the quadruplex community's attention to the cytosine (C)-rich complementary strands that can adopt unique tetra-stranded conformation, termed as intercalated motif or i-motif. I-motifs are stabilized by hemi-protonated C:CH+ base pairs under acidic conditions. Initially, the in vivo occurrence of i-motifs was underestimated because their formation is favored at non-physiological pH. However, groundbreaking research utilizing the structure-specific iMab antibody and high-throughput sequencing have recently detected their conserved dispersion throughout the genome, challenging previous assumptions. Given the evolving nature of this research field, it becomes imperative to conduct independent in vitro experiments aimed at identifying potential i-motif formation in C-rich sequences and consolidating the findings to address the properties of i-motifs. This chapter serves as an introductory guide for the swift identification of novel i-motifs, where we present an experimental framework for investigating and characterizing i-motif sequences in vitro. In this chapter, we selected a synthetic oligonucleotide (C7T3) sequence and outlined appropriate methodologies for annealing the i-motif structure into suitable buffers. Then, we validated its formation by CD (Circular Dichroism) and NMR (Nuclear Magnetic Resonance) spectroscopy. Finally, we provided a thorough account of the step-by-step procedures to investigate the effect of i-motif formation on the stalling or retardation of DNA replication using high resolution primer extension assays.

Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Serie
Methods in enzymology, ISSN 0076-6879 ; 693
Nyckelord
Circular dichroism, I-motifs, Nuclear magnetic resonance, Primer extension assay, Quadruplex DNA
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-218112 (URN)10.1016/bs.mie.2023.11.001 (DOI)2-s2.0-85178602961 (Scopus ID)
Forskningsfinansiär
Cancerfonden, 22 2380 Pj 01HVetenskapsrådet, VR-MH 2021-02468Knut och Alice Wallenbergs Stiftelse, KAW 2021.0173Kempestiftelserna, SMK2058Wenner-Gren Stiftelserna, o.UPD2020-0097Åke Wibergs Stiftelse, M20-0125
Tillgänglig från: 2023-12-19 Skapad: 2023-12-19 Senast uppdaterad: 2023-12-19
Deiana, M., Andrés Castán, J. M., Josse, P., Kahsay, A., Sánchez, D. P., Morice, K., . . . Sabouri, N. (2023). A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression. Nucleic Acids Research, 51(12), 6264-6285
Öppna denna publikation i ny flik eller fönster >>A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression
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2023 (Engelska)Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 51, nr 12, s. 6264-6285Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2023
Nationell ämneskategori
Biokemi och molekylärbiologi Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-212227 (URN)10.1093/nar/gkad365 (DOI)000988008500001 ()37191066 (PubMedID)2-s2.0-85164253573 (Scopus ID)
Forskningsfinansiär
Cancerfonden, 22 2380 PjVetenskapsrådet, VR-MH 2021–02468Knut och Alice Wallenbergs Stiftelse, KAW 2021-0173Cancerfonden, 21 0302 PT 01 HWenner-Gren Stiftelserna, UPD2020-0097Cancerfonden, 20 0827 PjFCancerforskningsfonden i Norrland, LP 22-2312Cancerforskningsfonden i Norrland, LP20 1024 2257Cancerforskningsfonden i Norrland, LP 21–2298Vetenskapsrådet, 2017-01531Svenska läkaresällskapet, SLS-890521Region Västerbotten, RV-930167SjöbergstiftelsenKnut och Alice Wallenbergs Stiftelse, KAW 2015.0114Marianne och Marcus Wallenbergs Stiftelse, MMW 2020.0189Cancerfonden, 20 1339 PjF
Tillgänglig från: 2023-07-21 Skapad: 2023-07-21 Senast uppdaterad: 2023-07-21Bibliografiskt granskad
Deiana, M., Chand, K., Chorell, E. & Sabouri, N. (2023). Parallel G-quadruplex DNA structures from nuclear and mitochondrial genomes trigger emission enhancement in a nonfluorescent nano-aggregated fluorine-boron-based dye. Journal of Physical Chemistry Letters, 14(7), 1862-1869
Öppna denna publikation i ny flik eller fönster >>Parallel G-quadruplex DNA structures from nuclear and mitochondrial genomes trigger emission enhancement in a nonfluorescent nano-aggregated fluorine-boron-based dye
2023 (Engelska)Ingår i: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 14, nr 7, s. 1862-1869Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Molecular self-assembly is a powerful tool for the development of functional nanostructures with adaptive optical properties. However, in aqueous solution, the hydrophobic effects in the monomeric units often afford supramolecular architectures with typical side-by-side π-stacking arrangement with compromised emissive properties. Here, we report on the role of parallel DNA guanine quadruplexes (G4s) as supramolecular disaggregating-capture systems capable of coordinating a zwitterionic fluorine-boron-based dye and promoting activation of its fluorescence signal. The dye's high binding affinity for parallel G4s compared to nonparallel topologies leads to a selective disassembly of the dye's supramolecular state upon contact with parallel G4s. This results in a strong and selective disaggregation-induced emission that signals the presence of parallel G4s observable by the naked eye and inside cells. The molecular recognition strategy reported here will be useful for a multitude of affinity-based applications with potential in sensing and imaging systems.

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2023
Nationell ämneskategori
Fysikalisk kemi
Identifikatorer
urn:nbn:se:umu:diva-205385 (URN)10.1021/acs.jpclett.2c03301 (DOI)000936590300001 ()36779779 (PubMedID)2-s2.0-85148521026 (Scopus ID)
Tillgänglig från: 2023-03-10 Skapad: 2023-03-10 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Jamroskovic, J., Deiana, M. & Sabouri, N. (2022). Probing the folding pathways of four-stranded intercalated cytosine-rich motifs at single base-pair resolution. Biochimie, 199, 81-91
Öppna denna publikation i ny flik eller fönster >>Probing the folding pathways of four-stranded intercalated cytosine-rich motifs at single base-pair resolution
2022 (Engelska)Ingår i: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 199, s. 81-91Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Cytosine-rich DNA can fold into four-stranded intercalated structures called i-motifs (iMs) under acidic conditions through the formation of hemi-protonated C:C+ base pairs. However, the folding and stability of iMs rely on many other factors that are not yet fully understood. Here, we combined biochemical and biophysical approaches to determine the factors influencing iM stability under a wide range of experimental conditions. By using high-resolution primer extension assays, circular dichroism, and absorption spectroscopies, we demonstrate that the stabilities of three different biologically relevant iMs are not dependent on molecular crowding agents. Instead, some of the crowding agents affected overall DNA synthesis. We also tested a range of small molecules to determine their effect on iM stabilization at physiological temperature and demonstrated that the G-quadruplex-specific molecule CX-5461 is also a promising candidate for selective iM stabilization. This work provides important insights into the requirements needed for different assays to accurately study iM stabilization, which will serve as important tools for understanding the contribution of iMs in cell regulation and their potential as therapeutic targets.

Ort, förlag, år, upplaga, sidor
Elsevier, 2022
Nyckelord
CX-5461, DNA replication, G-quadruplex DNA, High-resolution primer extension assay, I-motif DNA, pH
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-194635 (URN)10.1016/j.biochi.2022.04.007 (DOI)000800388200003 ()35452743 (PubMedID)2-s2.0-85129038456 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2021-02468Cancerfonden, 2019/126Åke Wibergs Stiftelse, M20-0125Cancerfonden, 21 0302 PT 01 H
Tillgänglig från: 2022-05-12 Skapad: 2022-05-12 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Deiana, M., Josse, P., Dalinot, C., Osmolovskyi, A., Marqués, P. S., Castán, J. M., . . . Cabanetos, C. (2022). Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy. Communications Chemistry, 5, Article ID 142.
Öppna denna publikation i ny flik eller fönster >>Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy
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2022 (Engelska)Ingår i: Communications Chemistry, E-ISSN 2399-3669, Vol. 5, artikel-id 142Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Photodynamic therapy is a clinically approved anticancer modality that employs a light-activated agent (photosensitizer) to generate cytotoxic reactive oxygen species (ROS). There is therefore a growing interest for developing innovative photosensitizing agents with enhanced phototherapeutic performances. Herein, we report on a rational design synthetic procedure that converts the ultrabright benzothioxanthene imide (BTI) dye into three heavy-atom-free thionated compounds featuring close-to-unit singlet oxygen quantum yields. In contrast to the BTI, these thionated analogs display an almost fully quenched fluorescence emission, in agreement with the formation of highly populated triplet states. Indeed, the sequential thionation on the BTI scaffold induces torsion of its skeleton reducing the singlet-triplet energy gaps and enhancing the spin-orbit coupling. These potential PSs show potent cancer-cell ablation under light irradiation while remaining non-toxic under dark condition owing to a photo-cytotoxic mechanism that we believe simultaneously involves singlet oxygen and superoxide species, which could be both characterized in vitro. Our study demonstrates that this simple site-selected thionated platform is an effective strategy to convert conventional carbonyl-containing fluorophores into phototherapeutic agents for anticancer PDT.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2022
Nationell ämneskategori
Biofysik
Identifikatorer
urn:nbn:se:umu:diva-200995 (URN)10.1038/s42004-022-00752-x (DOI)000876981400002 ()2-s2.0-85140992916 (Scopus ID)
Forskningsfinansiär
Cancerfonden, 21 0302 PT 01 HCancerfonden, 2019/126Vetenskapsrådet, 2021-02468EU, Horisont 2020, 722651
Anmärkning

We acknowledge the Biochemical Imaging Center at Umeå University and the National Microscopy Infrastructure, NMI (VR-RFI 2019-00217) for providing assistance in microscopy.

Tillgänglig från: 2022-11-17 Skapad: 2022-11-17 Senast uppdaterad: 2022-11-17Bibliografiskt granskad
Deiana, M., Obi, I., Andréasson, M., Tamilselvi, S., Chand, K., Chorell, E. & Sabouri, N. (2021). A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures. ACS Chemical Biology, 16(8), 1365-1376
Öppna denna publikation i ny flik eller fönster >>A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures
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2021 (Engelska)Ingår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 16, nr 8, s. 1365-1376Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

G-quadruplex (G4) DNA structures are widespread in the human genome and are implicated in biologically important processes such as telomere maintenance, gene regulation, and DNA replication. Guanine-rich sequences with potential to form G4 structures are prevalent in the promoter regions of oncogenes, and G4 sites are now considered as attractive targets for anticancer therapies. However, there are very few reports of small “druglike” optical G4 reporters that are easily accessible through one-step synthesis and that are capable of discriminating between different G4 topologies. Here, we present a small water-soluble light-up fluorescent probe that features a minimalistic amidinocoumarin-based molecular scaffold that selectively targets parallel G4 structures over antiparallel and non-G4 structures. We showed that this biocompatible ligand is able to selectively stabilize the G4 template resulting in slower DNA synthesis. By tracking individual DNA molecules, we demonstrated that the G4-stabilizing ligand perturbs DNA replication in cancer cells, resulting in decreased cell viability. Moreover, the fast-cellular entry of the probe enabled detection of nucleolar G4 structures in living cells. Finally, insights gained from the structure–activity relationships of the probe suggest the basis for the recognition of parallel G4s, opening up new avenues for the design of new biocompatible G4-specific small molecules for G4-driven theranostic applications.

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2021
Nationell ämneskategori
Läkemedelskemi Biokemi och molekylärbiologi Biofysik
Identifikatorer
urn:nbn:se:umu:diva-187118 (URN)10.1021/acschembio.1c00134 (DOI)000697396400009 ()34328300 (PubMedID)2-s2.0-85113337330 (Scopus ID)
Forskningsfinansiär
Kempestiftelserna, SMK-1632Knut och Alice Wallenbergs Stiftelse, KAW2015-0189Cancerfonden, CAN 2019/126Vetenskapsrådet, 2017-05235Vetenskapsrådet, 2018-02651
Tillgänglig från: 2021-09-01 Skapad: 2021-09-01 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
Deiana, M., Mosser, M., Le Bahers, T., Dumont, E., Dudek, M., Denis-Quanquin, S., . . . Guy, L. (2021). Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures. Nanoscale, 13(32), 13795-13808
Öppna denna publikation i ny flik eller fönster >>Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures
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2021 (Engelska)Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 13, nr 32, s. 13795-13808Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Light-activated functional materials capable of remote control over duplex and G-quadruplex (G4) nucleic acids formation at the cellular level are still very rare. Herein, we report on the photoinduced macrocyclisation of a helicenoid quinoline derivative of binaphthol that selectively provides easy access to an unprecedented class of extended heteroaromatic structures with remarkable photophysical and DNA/RNA binding properties. Thus, while the native bisquinoline precursor shows no DNA binding activity, the new in situ photochemically generated probe features high association constants to DNA and RNA G4s. The latter inhibits DNA synthesis by selectively stabilizing G4 structures associated with oncogenic promoters and telomere repeat units. Finally, the light sensitive compound is capable of in cellulo photoconversion, localizes primarily in the G4-rich sites of cancer cells, competes with a well-known G4 binder and shows a clear nuclear co-localization with the quadruplex specific antibody BG4. This work provides a benchmark for the future design and development of a brand-new generation of light-activated target-selective G4-binders.

Ort, förlag, år, upplaga, sidor
Royal Society of Chemistry, 2021
Nationell ämneskategori
Biofysik Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:umu:diva-187087 (URN)10.1039/d1nr02855c (DOI)000680884100001 ()34477654 (PubMedID)2-s2.0-85113310558 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018-02651Knut och Alice Wallenbergs Stiftelse, KAW2015-0189Cancerfonden, 2019/126
Anmärkning

Correction: Light-induced in situ chemicalactivation of a fluorescent probe for monitoringintracellular G-quadruplex structures. Nanoscale, 2023, 15, 388. DOI: 10.1039/d2nr90225g

Tillgänglig från: 2021-09-03 Skapad: 2021-09-03 Senast uppdaterad: 2022-12-29Bibliografiskt granskad
Yan, K.-P., Obi, I. & Sabouri, N. (2021). The RGG domain in the C-terminus of the DEAD box helicases Dbp2 and Ded1 is necessary for G-quadruplex destabilization. Nucleic Acids Research, 49(14), 8339-8354
Öppna denna publikation i ny flik eller fönster >>The RGG domain in the C-terminus of the DEAD box helicases Dbp2 and Ded1 is necessary for G-quadruplex destabilization
2021 (Engelska)Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 49, nr 14, s. 8339-8354Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The identification of G-quadruplex (G4) binding proteins and insights into their mechanism of action are important for understanding the regulatory functions of G4 structures. Here, we performed an unbiased affinity-purification assay coupled with mass spectrometry and identified 30 putative G4 binding proteins from the fission yeast Schizosaccharomyces pombe. Gene ontology analysis of the molecular functions enriched in this pull-down assay included mRNA binding, RNA helicase activity, and translation regulator activity. We focused this study on three of the identified proteins that possessed putative arginine-glycine-glycine (RGG) domains, namely the Stm1 homolog Oga1 and the DEAD box RNA helicases Dbp2 and Ded1. We found that Oga1, Dbp2, and Ded1 bound to both DNA and RNA G4s in vitro. Both Dbp2 and Ded1 bound to G4 structures through the RGG domain located in the C-terminal region of the helicases, and point mutations in this domain weakened the G4 binding properties of the helicases. Dbp2 and Ded1 destabilized less thermostable G4 RNA and DNA structures, and this ability was independent of ATP but dependent on the RGG domain. Our study provides the first evidence that the RGG motifs in DEAD box helicases are necessary for both G4 binding and G4 destabilization.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2021
Nationell ämneskategori
Cell- och molekylärbiologi Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-187116 (URN)10.1093/nar/gkab620 (DOI)000692599800043 ()34302476 (PubMedID)2-s2.0-85114315622 (Scopus ID)
Forskningsfinansiär
Wenner-Gren StiftelsernaKnut och Alice Wallenbergs Stiftelse
Tillgänglig från: 2021-09-01 Skapad: 2021-09-01 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Deiana, M., Chand, K., Jamroskovic, J., Obi, I., Chorell, E. & Sabouri, N. (2020). A Light‐up Logic Platform for Selective Recognition of Parallel G‐Quadruplex Structures via Disaggregation‐Induced Emission. Angewandte Chemie International Edition, 59(2), 896-902
Öppna denna publikation i ny flik eller fönster >>A Light‐up Logic Platform for Selective Recognition of Parallel G‐Quadruplex Structures via Disaggregation‐Induced Emission
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2020 (Engelska)Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 59, nr 2, s. 896-902Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The design of turn‐on dyes with optical signals sensitive to the formation of supramolecular structures provides fascinating and underexplored opportunities for G‐quadruplex (G4) DNA detection and characterization. Here, we show a new switching mechanism that relies on the recognition‐driven disaggregation (on‐signal) of an ultrabright coumarin‐quinazoline conjugate. The synthesized probe selectively lights‐up parallel G4 DNA structures via the disassembly of its supramolecular state, demonstrating outputs that are easily integrable into a label free molecular logic system. Finally, our molecule preferentially stains the G4‐rich nucleoli of cancer cells.

Ort, förlag, år, upplaga, sidor
Wiley-VCH Verlagsgesellschaft, 2020
Nyckelord
aggregation, biosensor, DNA, G-quadruplex, logic gate
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
medicinsk biokemi
Identifikatorer
urn:nbn:se:umu:diva-164662 (URN)10.1002/anie.201912027 (DOI)000497789300001 ()31644837 (PubMedID)2-s2.0-85075533982 (Scopus ID)
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, KAW2015-0189Vetenskapsrådet, VR-NT 2017-05235Vetenskapsrådet, VR-MH 2018-02651Kempestiftelserna, SMK-1632
Tillgänglig från: 2019-10-25 Skapad: 2019-10-25 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Deiana, M., Chand, K., Jamroskovic, J., Das, R. N., Obi, I., Chorell, E. & Sabouri, N. (2020). A Site-Specific Self-Assembled Light-up Rotor Probe for Selective Recognition and Stabilization of c-MYC G-Quadruplex DNA. Nanoscale, 12(24), 12950-12957
Öppna denna publikation i ny flik eller fönster >>A Site-Specific Self-Assembled Light-up Rotor Probe for Selective Recognition and Stabilization of c-MYC G-Quadruplex DNA
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2020 (Engelska)Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 12, nr 24, s. 12950-12957Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Royal Society of Chemistry, 2020
Nationell ämneskategori
Biokemi och molekylärbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Organisk kemi Fysikalisk kemi
Forskningsämne
biokemi; organisk kemi; fysikalisk kemi; cellforskning
Identifikatorer
urn:nbn:se:umu:diva-171513 (URN)10.1039/D0NR03404E (DOI)000545599900025 ()2-s2.0-85087110627 (Scopus ID)
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, KAW2015-0189Vetenskapsrådet, VR-NT 2017-05235Vetenskapsrådet, VR-MH 2018-02651Kempestiftelserna, SMK-1632
Tillgänglig från: 2020-06-03 Skapad: 2020-06-03 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Projekt
Det essentiella helikaset Pfh1s roll i arvsmassans integritet [2012-03087_VR]; Umeå universitetDen fyrsträngade DNA strukturens roll i hälsa och sjukdom [2018-02651_VR]; Umeå universitet
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-4541-7702

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