Stabilizing Parallel G-Quadruplex DNA by A New Class of Ligands: Two Non-planar Alkaloids through Interaction in Lateral Grooves
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 π-π stacking. However, based on a pharmacophore-based virtual screening (Catalyst, Accelrys) 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.
Qian Li Aijiao Guan Qianfan Yang Shu Yang Guangzhi Xu Junfeng Xiang Xudong Li Xiaojie Xu Yalin Tang Qiuju Zhou Lin Li Hong Zhang Hongxia Sun
Beijing National Laboratory for Molecular Sciences (BNLMS), Center for Molecular Sciences, State Key Beijing National Laboratory for Molecular Sciences (BNLMS), Center for Molecular Sciences, State Key Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Lab of Rare Earth Material Che
国际会议
武汉
英文
468-496
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）