Nuclear magnetic resonance studies reveal stabilization of parallel G-quadruplex DNA [d(T2G4T)]4upon binding to protoberberine alkaloid coralyne.
Stabilization of G-quadruplex DNA structures in human telomeric and proto-oncogenic promoter regions upon ligand binding has evolved as a viable anti-cancer strategy. We have studied interaction of coralyne, a human telomerase inhibiting protoberberine alkaloid, with parallel stranded tetrameric G-quadruplex DNA [d(T2G4T)]4using Circular Dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Appearance of induced CD band and the Diffusion Ordered NMR Spectroscopy (DOSY) experiments confirm the formation of well defined coralyne-DNA complex.1H and31P NMR studies reveal that coralyne specifically recognizes T2pG3 and G6pT7 steps in DNA. Guanine imino protons indicate that coralyne binding induces thermal stabilization of the G-quadruplex DNA by >20°C. The observed specific changes and thermal stabilization of DNA upon binding may be attributed to inhibition of telomerase by coralyne.
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.
Kumar
K
Padmapriya
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India. Electronic address: ritubfbs@iitr.ac.in.
Ritu
R
Barthwal
D001600:Berberine Alkaloids / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*
D001600:Berberine Alkaloids; C000666:coralyne; D004247:DNA
Alkaloid; Circular Dichroism; Coralyne; G-quadruplex DNA; Nuclear magnetic resonance; Thermal stabilization