Structurally diverse G-quadruplexes as the noncanonical nucleic acid drug target for live cell imaging and antibacterial study

Zheng, Bo-Xin; Yu, Jie; Long, Wei; Chan, Ka Hin; Leung, Alan Siu-Lun; Wong, Wing‐Leung

doi:10.1039/d2cc05945b

Cited by 11 publications

(11 citation statements)

References 213 publications

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“…Currently, the reported small molecule‐based fluorescent probes targeting RNA and DNA secondary structures are mostly with emission in the visible light region ranged from 450–650 nm while the probe emitting in the range of 660–750 nm is not common [20a,b,22a,c] . This may imply that the development of red or NIR fluorescent probes for RNA imaging is challenging and more efforts may be required for further advancement in the future.…”

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

“…As a biosensor for imaging and real‐time monitoring of the RNA target of interest in live cells, apart from the selectivity and sensitivity of the probe, the water solubility, cytotoxicity, fluorescence quantum yield and intracellular photostability are important parameters determining the performance of the probe in live cell imaging. It seems that most RNA‐selective ligands developed are excited in the visible light region (400–600 nm) [20a,b,22a,d] . However, for in vivo studies, the tissue penetration ability of the light source required to excite the ligand may be an important factor of consideration.…”

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

“…The RNA G4‐selective fluorescent ligands with the use of advanced fluorescence microscopy techniques may provide a powerful tool for in‐depth investigations. Currently, there are just a few X ‐ray crystal structures of RNA G4 structures reported and thus their structural information is very limited at present [20a,57] . It is therefore an challenge task for molecular chemists to design highly selective fluorescent ligands targeting RNA G4‐structures.…”

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

“…It is therefore an challenge task for molecular chemists to design highly selective fluorescent ligands targeting RNA G4‐structures. Nonetheless, about fourteen fluorescent ligands shown in Figure 5 have been reported currently and most of them have been reviewed over the past two years [20a,b,46b] …”

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

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RNA‐Selective Small‐Molecule Ligands: Recent Advances in Live‐Cell Imaging and Drug Discovery

Chan,

Wang,

Zheng

et al. 2023

ChemMedChem

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RNA structures, including those formed from coding and noncoding RNAs, alternative to protein‐based drug targets, could be a promising target of small molecules for drug discovery against various human diseases, particularly in anticancer, antibacterial and antivirus development. The normal cellular activity of cells is critically dependent on the function of various RNA molecules generated from DNA transcription. Moreover, many studies support that mRNA‐targeting small molecules may regulate the synthesis of disease‐related proteins via the non‐covalent mRNA‐ligand interactions that do not involve gene modification. RNA‐ligand interaction is thus an attractive approach to address the challenge of “undruggable” proteins in drug discovery because the intracellular activity of these proteins is hard to be suppressed with small molecule ligands. We selectively surveyed a specific area of RNA structure‐selective small molecule ligands in fluorescence live cell imaging and drug discovery because the area was currently underexplored. This state‐of‐the‐art review thus mainly focuses on the research published within the past three years and aims to provide the most recent information on this research area; hopefully, it could be complementary to the previously reported reviews and give new insights into the future development on RNA‐specific small molecule ligands for live cell imaging and drug discovery.

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Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

Section: Fluorescent Imaging Of Cellular Rnas With Small‐molecule Lig...mentioning

confidence: 99%

See 2 more Smart Citations

RNA‐Selective Small‐Molecule Ligands: Recent Advances in Live‐Cell Imaging and Drug Discovery

Chan,

Wang,

Zheng

et al. 2023

ChemMedChem

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“…Non-B DNA secondary structures play many roles in vivo , such as Holliday junctions in recombination and slipped structures in mutagenesis. − Most recently, G-quadruplexes were proposed to play an important role in telomere maintenance and modulating transcription and translation, as well as causing genome instability. − Unfortunately, most non-B DNA structures exist transiently in vivo and are difficult to detect and locate. Small-molecule and antibody probes for detecting G-quadruplexes in vivo have been reported, − some of which drive the formation of the structures that they seek to probe and/or require fixation of the cells, which chemically alters the DNA . Many of the probes also bind to multiple G-quadruplex conformations with varying selectivity.…”

Section: Introductionmentioning

confidence: 99%

Post- and Pre-Radiolabeling Assays for anti Thymidine Cyclobutane Dimers as Intrinsic Photoprobes of Various Types of G-Quadruplexes, Reverse Hoogsteen Hairpins, and Other Non-B DNA Structures

Gutierrez-Bayona,

Scruggs,

Yang

et al. 2023

Biochemistry

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G-quadruplexes are thought to play an important role in gene regulation and telomere maintenance, but developing probes for their presence and location is challenging due to their transitory and highly dynamic nature. The majority of probes for G-quadruplexes have relied on antibody or small-molecule binding agents, many of which can also alter the dynamics and relative populations of G-quadruplexes. Recently, it was discovered that ultraviolet B (UVB) irradiation of human telomeric DNA and various G-quadruplex forming sequences found in human promoters, as well as reverse Hoogsteen hairpins, produces a unique class of non-adjacent anti cyclobutane pyrimidine dimers (CPDs). Therefore, one can envision using a pulse of UVB light to irreversibly trap these non-B DNA structures via anti CPD formation without perturbing their dynamics, after which the anti CPDs can be identified and mapped. As a first step toward this goal, we report radioactive post- and pre-labeling assays for the detection of non-adjacent CPDs and illustrate their use in detecting trans,anti T=(T) CPD formation in a human telomeric DNA sequence. Both assays make use of snake venom phosphodiesterase (SVP) to degrade the trans,anti T=(T) CPD-containing DNA to the tetranucleotide pTT=(pTT) corresponding to CPD formation between the underlined T′s of two separate dinucleotides while degrading the adjacent syn TT CPDs to the trinucleotide pGT=T. In the post-labeling assay, calf intestinal phosphodiesterase is used to dephosphorylate the tetranucleotides, which are then rephosphorylated with kinase and [32P]-ATP to produce radiolabeled mono- and diphosphorylated tetranucleotides. The tetranucleotides are confirmed to be non-adjacent CPDs by 254 nm photoreversion to the dinucleotide p*TT. In the pre-labeling assay, radiolabeled phosphates are introduced into non-adjacent CPD-forming sites by ligation prior to irradiation, thereby eliminating the dephosphorylation and rephosphorylation steps. The assays are also demonstrated to detect the stereoisomeric cis,anti T=(T) CPD.

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A Cytoplasm‐Specific Fluorescent Ligand for Selective Imaging of RNA G‐Quadruplexes in Live Cancer Cells

Zheng

Long

She

et al. 2023

Chemistry A European J

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The development of site‐specific, target‐selective and biocompatible small molecule ligands as a fluorescent tool for real‐time study of cellular functions of RNA G‐quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm‐specific and RNA G4‐selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA. These G4s are recognized as human cancer hallmarks. Moreover, intracellular competition studies with BRACO19 and PDS, and the colocalization study with G4‐specific antibody (BG4) in HeLa cells may support that the ligand selectively binds to G4s in cellulo. Furthermore, the ligand was demonstrated for the first time in the visualization and monitoring of dynamic resolving process of RNA G4s by the overexpressed RFP‐tagged DHX36 helicase in live HeLa cells.

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Structurally diverse G-quadruplexes as the noncanonical nucleic acid drug target for live cell imaging and antibacterial study

Abstract: The formation of G-quadruplex structures (G4s) in vitro from guanine (G)-rich nucleic acid sequences of DNA and RNA stabilized with monovalent cations, typically K+ and Na+, under physiological conditions, have...

Cited by 11 publications

References 213 publications

RNA‐Selective Small‐Molecule Ligands: Recent Advances in Live‐Cell Imaging and Drug Discovery

RNA‐Selective Small‐Molecule Ligands: Recent Advances in Live‐Cell Imaging and Drug Discovery

Post- and Pre-Radiolabeling Assays for anti Thymidine Cyclobutane Dimers as Intrinsic Photoprobes of Various Types of G-Quadruplexes, Reverse Hoogsteen Hairpins, and Other Non-B DNA Structures

A Cytoplasm‐Specific Fluorescent Ligand for Selective Imaging of RNA G‐Quadruplexes in Live Cancer Cells

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