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Updated: Mar 21, 2026
Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping
Published on: May 12, 2023
Interaction of KRAS G-quadruplex with natural polyphenols: A spectroscopic analysis with molecular modeling
Rudradip Pattanayak1, Pijush Basak1, Srikanta Sen2
1Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
Abstract:
Researchers are endeavoring to find out new therapeutics for curing cancer and G-quadruplex DNA has already been identified as a prospective one in this venture. Stabilizing G-quadruplex structures of telomere has emerged to be an important strategy in this context. Mutation in KRAS is mostly responsible for pancreatic, lung and colon cancer. In this present study we explored binding and conformational behaviour of G-quadruplex with different ligands by utilizing several biophysical techniques. Natural polyphenols like Curcumin and Ellagic acid were observed to bind with the G-quadruplex and enhance the melting temperature significantly indicating higher stability. UV-vis spectroscopy confirms formation of G quadruplex-ligand complex for both the compounds with specific binding affinity. Fluorimetric studies revealed that Ellagic acid had stronger binding affinity, 1.10×10(5)M(-1) compared to Curcumin, 1.6×10(4)M(-1) towards G-quadruplex. Interestingly, Curcumin provides greater stability by stacking on the top of the quadruplex structure with the help of the loops compared to Ellagic acid as is evident by docking studies. The keto form of curcumin showed stronger affinity than the enol form. We have developed a general model to estimate the influence of the ligands towards stabilizing the G-quadruplex subsequently characterizing the binding profile to enlighten prospective therapeutics.
Insights
Researchers explored how natural compounds like Curcumin and Ellagic acid stabilize G-quadruplex DNA, a potential cancer therapeutic target. Both compounds bind, with Ellagic acid showing higher affinity, while Curcumin offers greater structural stability.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- G-quadruplex DNA structures, particularly in telomeres, are promising targets for cancer therapeutics.
- Stabilizing these structures is a key strategy to inhibit cancer cell proliferation.
- KRAS mutations are significant drivers in pancreatic, lung, and colon cancers.
Purpose of the Study:
- To investigate the binding and conformational effects of natural polyphenols (Curcumin, Ellagic acid) on G-quadruplex DNA.
- To characterize the interaction profile and stability enhancement induced by these ligands.
- To develop a model for predicting ligand influence on G-quadruplex stabilization.
Main Methods:
- Biophysical techniques including UV-vis spectroscopy and fluorimetry.
- Melting temperature analysis to assess structural stability.
- Molecular docking studies to elucidate binding modes.
Main Results:
- Curcumin and Ellagic acid bind to G-quadruplex DNA, significantly increasing its melting temperature and stability.
- UV-vis spectroscopy confirmed G-quadruplex-ligand complex formation with specific binding affinities.
- Ellagic acid exhibited stronger binding affinity (1.10×10^5 M⁻¹) than Curcumin (1.6×10^4 M⁻¹).
- Docking studies indicated Curcumin provides superior stability through loop stacking interactions.
Conclusions:
- Natural polyphenols Curcumin and Ellagic acid effectively bind and stabilize G-quadruplex DNA.
- Curcumin's keto form demonstrates stronger binding affinity than its enol form.
- These findings provide a foundation for developing novel G-quadruplex-targeting cancer therapeutics.
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