Nuclear magnetic resonance studies reveal stabilization of parallel G-quadruplex DNA [d(T2G4T)]4 upon binding to protoberberine alkaloid coralyne

被引:10
作者
Padmapriya, Kumar [1 ]
Barthwal, Ritu [1 ]
机构
[1] Indian Inst Technol Roorkee, Dept Biotechnol, Roorkee 247667, Uttar Pradesh, India
关键词
G-quadruplex DNA; Coralyne; Alkaloid; Circular Dichroism; Nuclear magnetic resonance; Thermal stabilization; STRANDED G-QUADRUPLEX; TELOMERIC SEQUENCE; ACTINOMYCIN-D; P-31; NMR; INTERCALATION; DUPLEX; ACID; RECOGNITION; DERIVATIVES; DISTAMYCIN;
D O I
10.1016/j.bmcl.2016.09.016
中图分类号
R914 [药物化学];
学科分类号
100701 ;
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.
引用
收藏
页码:4915 / 4918
页数:4
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