Environment‐Sensitive Probes Containing a 2,6‐Diethynylpyridine Motif for Fluorescence Turn‐On Detection and Induction of Nanoarchitectures of Human Telomeric Quadruplex

Das, Rabindra Nath; Debnath, Manish; Gaurav, Abhiket

doi:10.1002/chem.201404795

Cited by 11 publications

(6 citation statements)

References 68 publications

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“…We observed that the emission maximum of BTC f is blue-shifted from 522 to 410 nm and the fluorescence intensity is simultaneously enhanced as the solvent polarity decreases from water to ethylacetate. These observations suggest that the enhancement in the fluorescence intensity along with the blue-shift in the emission spectra of the BTC f with the quadruplexes is a consequence of the proximity of BTC f to the non-polar hydrophobic regions 35 of the G-quadruplexes thereby manifesting the high affinity of BTC f towards the G-quadruplex structures.…”

Section: Resultsmentioning

confidence: 88%

A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of c-MYC G-quadruplex and Down-regulates c-MYC Transcription in Human Cancer Cells

Panda

Debnath

Mandal

et al. 2015

Sci Rep

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The c-MYC proto-oncogene is a regulator of fundamental cellular processes such as cell cycle progression and apoptosis. The development of novel c-MYC inhibitors that can act by targeting the c-MYC DNA G-quadruplex at the level of transcription would provide potential insight into structure-based design of small molecules and lead to a promising arena for cancer therapy. Herein we report our finding that two simple bis-triazolylcarbazole derivatives can inhibit c-MYC transcription, possibly by stabilizing the c-MYC G-quadruplex. These compounds are prepared using a facile and modular approach based on Cu(I) catalysed azide and alkyne cycloaddition. A carbazole ligand with carboxamide side chains is found to be microenvironment-sensitive and highly selective for “turn-on” detection of c-MYC quadruplex over duplex DNA. This fluorescent probe is applicable to visualize the cellular nucleus in living cells. Interestingly, the ligand binds to c-MYC in an asymmetric fashion and selects the minor-populated conformer via conformational selection.

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Section: Resultsmentioning

confidence: 88%

A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of c-MYC G-quadruplex and Down-regulates c-MYC Transcription in Human Cancer Cells

Panda

Debnath

Mandal

et al. 2015

Sci Rep

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“…83 BPEP 1 is a bis(phenyethynyl)pyridylcarboxamide compound. 84 CV refers to Crystal violet; ThT to Thioflavin T. c ex -NDI is an extended naphthalene diimide derivative specific for parallel G-quadruplexes. 81 Hemin is a natural G-quadruplex ligand found in DNAzymes (see section 6.3).…”

Section: Ligandsmentioning

confidence: 99%

“…Spectroscopic data suggest an intercalative mechanism of cationic porphyrin binding to potassium-free G-wires; such a binding mode, expectedly, is absent when dealing with the potassium form of this G-wire. 135 Das et al 84 have reported interesting data showing that certain end-stacking bis(phenyethynyl)pyridylcarboxamide (BPEP) ligands assist the formation of G-wires by mixed-topology intramolecular G4 units formed by the human/vertebrate telomeric repeat (T 2 AG 3 ) 4 (h-TELO). The authors hypothesized that these ligands end-stack at either end of individual intramolecular h-TELO quadruplex units and help to join together such individual units to generate long wires.…”

Section: G4 Ligands Binding To G-wiresmentioning

confidence: 99%

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DNA Quadruple Helices in Nanotechnology

2019

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DNA has played an early and powerful role in the development of bottomup nanotechnologies, not least because of DNA's precise, predictable, and controllable properties of assembly on the nanometer scale. Watson−Crick complementarity has been used to build complex 2D and 3D architectures and design a number of nanometer-scale systems for molecular computing, transport, motors, and biosensing applications. Most of such devices are built with classical B-DNA helices and involve classical A-T/U and G-C base pairs. However, in addition to the above components underlying the iconic double helix, a number of alternative pairing schemes of nucleobases are known. This review focuses on two of these noncanonical classes of DNA helices: G-quadruplexes and the imotif. The unique properties of these two classes of DNA helix have been utilized toward some remarkable constructions and applications: G-wires; nanostructures such as DNA origami; reconfigurable structures and nanodevices; the formation and utilization of hemin-utilizing DNAzymes, capable of generating varied outputs from biosensing nanostructures; composite nanostructures made up of DNA as well as inorganic materials; and the construction of nanocarriers that show promise for the therapeutics of diseases.

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“…6d–i). Fluorescence binding titration revealed that these carbazole derivatives are environmentally sensitive probes for the G-quadruplex3640. The major lead compound Tz 1 exhibited a selective fluorescence enhancement (3.7-fold) upon binding with G-quadruplex with a 33 nm blueshift, whereas it barely showed any enhancement upon titration with duplex DNA.…”

Section: Resultsmentioning

confidence: 99%

Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

et al. 2017

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The development of small molecules is essential to modulate the cellular functions of biological targets in living system. Target Guided Synthesis (TGS) approaches have been used for the identification of potent small molecules for biological targets. We herein demonstrate an innovative example of TGS using DNA nano-templates that promote Huisgen cycloaddition from an array of azide and alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been prepared by assembling the DNA structures on gold-coated magnetic nanoparticles. The DNA nano-templates facilitate the regioselective formation of 1,4-substituted triazole products, which are easily isolated by magnetic decantation. The G-quadruplex nano-template can be easily recovered and reused for five reaction cycles. The major triazole product, generated by the G-quadruplex inhibits c-MYC expression by directly targeting the c-MYC promoter G-quadruplex. This work highlights that the nano-TGS approach may serve as a valuable strategy to generate target-selective ligands for drug discovery.

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Environment‐Sensitive Probes Containing a 2,6‐Diethynylpyridine Motif for Fluorescence Turn‐On Detection and Induction of Nanoarchitectures of Human Telomeric Quadruplex

Cited by 11 publications

References 68 publications

A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of c-MYC G-quadruplex and Down-regulates c-MYC Transcription in Human Cancer Cells

A Nucleus-Imaging Probe That Selectively Stabilizes a Minor Conformation of c-MYC G-quadruplex and Down-regulates c-MYC Transcription in Human Cancer Cells

DNA Quadruple Helices in Nanotechnology

Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

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