Stabilizing parallel G-quadruplex DNA by a new class of ligands: Two non-planar alkaloids through interaction in lateral grooves

被引：66

作者：

Li, Qian ^{[1
,3
]}

Xiang, Junfeng ^{[1
]}

Li, Xudong ^{[2
]}

Chen, Lirong ^{[2
]}

Xu, Xiaojie ^{[2
]}

Tang, Yalin ^{[1
]}

Zhou, Qiuju ^{[1
,3
]}

Li, Lin ^{[1
,3
]}

Zhang, Hong ^{[1
]}

Sun, Hongxia ^{[1
]}

Guan, Aijiao ^{[1
,3
]}

Yang, Qianfan ^{[1
,3
]}

Yang, Shu ^{[1
,3
]}

Xu, Guangzhi ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Chem, Ctr Mol Sci,BNLMS, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100190, Peoples R China

[2] Peking Univ, BNLMS, State Key Lab Rare Earth Mat Chem & Applicat, Coll Chem & Mol Engn, Beijing 100871, Peoples R China

[3] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China

来源：

BIOCHIMIE | 2009年 / 91卷 / 07期

关键词：

G-quadruplex; Groove binding; Non-planar; Alkaloids; ANTICANCER DRUG DESIGN; HUMAN TELOMERIC REPEAT; ANTITUMOR AGENTS; RECOGNITION; NMR; D(TTAGGGT)(4); INHIBITOR; TARGETS; POTENT; DERIVATIVES;

D O I：

10.1016/j.biochi.2009.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human DNA sequences consisting of tandem guanine (G) nucleotides can fold into a four-stranded structure named G-quadruplex via Hoogsteen hydrogen bonding. As the sequences forming G-quadruplex exist in essential regions of eukaryotic chromosomes and are involved in many important biological processes, the study of their biological functions has currently become a hotspot. Compounds selectively binding and stabilizing G-quadruplex structures have the potential to inhibit telomerase activity or alter oncogene expression levels and thus may act as antitumor agents. Most of reported G-quadruplex ligands generally have planar structures which stabilize G-quadruplex by pi-pi stacking. However, based on a pharmacophore-based virtual screening two non-planar G-quadruplex ligands were found. These two ligands exhibit good capability for G-quadruplex stabilization and prefer binding to paralleled G-quadruplex rather than to duplex DNA. The binding of these ligands to G-quadruplex may result from groove binding at a 2:1 stoichiometry. These results have shown that planar structures are not essential for G-quadruplex stabilizers, which may represent a new class of G-quadruplex-targeted agents as potential antitumor drugs. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：811 / 819

页数：9

共 41 条

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