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Binding Studies of Natural Product Berberine with DNA G-Quadruplex

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TLDR
Preliminary results showed that Berberine bind with this DNA strand in both pH conditions which is further supported by UV melting experiments, and this sequence can be used as probe to screen out tetraplex binding natural products which help to generate new anticancer drugs.
Abstract
Problem statement: The ends of chromosome had highly repetitive short G and C-rich sequences of DNA. These sequences were known to form stable tetraplex type of secondary structures which help to maintain gene integratity after cell divison. Approach: Any reagent which controls the random cell division would be useful to design anticancer drugs. Therefore a many natural and synthesized molecules which stabilized tetraplex structures are targeted as anticancer drug entities. Results: Among them, Berberine hydrochloride natural product and its analogues are well studies as G-quadruplex stabilizing agent. In this report, DNA sequence 5’-G3-C5-G3-3’ has been designed which has probability to form i-motif and G-qua druplex types of secondary structures. Herein we studied the interaction between this DNA strands and Berberine hydrochloride by 1H-NMR techniques and UV in two different PH (4.7 and 7.4) conditions. Conclusion/Recommendations: Our preliminary results showed that Berberine bind with this DNA strand in both pH conditions which is further supported by UV melting experiments. In future this sequence can be used as probe to screen out tetraplex binding natural products which help to generate new anticancer drugs.

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Citations
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Biophysical characterization of the strong stabilization of the RNA triplex poly(U)•poly(A)*poly(U) by 9-O-(ω-amino) alkyl ether berberine analogs.

TL;DR: Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berbers, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by theAlkyl side chain.
Journal ArticleDOI

Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex

TL;DR: Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G- quadruplexes.
References
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Journal ArticleDOI

Quadruplex DNA: sequence, topology and structure

TL;DR: This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence.
Journal ArticleDOI

Following G-quartet formation by UV-spectroscopy

TL;DR: It is shown that the recording of reversible absorbance changes at 295 nm allows to precisely monitor intramolecular guanine (G)‐quartet formation and dissociation.
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G-quadruplex nucleic acids as therapeutic targets

TL;DR: The highly distinctive nature of quadruplex topologies suggests that they can act as novel therapeutic targets, for example in the selective inhibition of transcription of a given oncogene, using designed small molecules to stabilise a particular quadruplex.
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Human telomeric DNA: G‐quadruplex, i‐motif and Watson–Crick double helix

TL;DR: Under near-physiological conditions of pH, temperature and salt concentration, telomeric DNA was predominantly in a double-helix form, however, at lower pH values or higher temperatures, the G-quadruplex and/or the i-motif efficiently competed with the duplex.
Journal ArticleDOI

Telomerase activity, cell proliferation, and cancer

TL;DR: The idea emerged that telomerase might be required for tumor growth in vivo and testing this idea has fed the exponential increase in telomersase papers in the past 5 years.
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