title: Interaction of KRAS G-quadruplex with natural polyphenols: A spectroscopic analysis with molecular modeling.
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.
authors.affiliation: Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
authors.forename: Rudradip
authors.initials: R
authors.lastname: Pattanayak
authors.affiliation: Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
authors.forename: Pijush
authors.initials: P
authors.lastname: Basak
authors.affiliation: Mira Tower, 229A/230, Lake Town, Block-A, Kolkata 700089, India.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India. Electronic address: bmaitree@gmail.com.
authors.forename: Maitree
authors.initials: M
authors.lastname: Bhattacharyya
mesh_terms: D001665:Binding Sites; D003474:Curcumin / Q000737:chemistry*; D004610:Ellagic Acid / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry*; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C117307:KRAS protein, human; D008024:Ligands; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D004610:Ellagic Acid; D016283:Proto-Oncogene Proteins p21(ras); D003474:Curcumin
keywords: Curcumin; Ellagic acid; G-quadruplex DNA; KRAS; Molecular docking