Nuclear magnetic resonance studies reveal stabilization of parallel G-quadruplex DNA [d(T(2)G(4)T)](4) upon binding to protoberberine alkaloid coralyne

摘要

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(T(2)G(4)T)](4) using 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. H-1 and P-31 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 degrees C. The observed specific changes and thermal stabilization of DNA upon binding may be attributed to inhibition of telomerase by coralyne. (C) 2016 Elsevier Ltd. All rights reserved.