Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry

doi:10.1002/rcm.6295

CORC > 化学研究所 > 中国科学院化学研究所

	Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry
	Cui, Xiaojie; Lin, Sen; Zhou, Jiang; Yuan, Gu
刊名	RAPID COMMUNICATIONS IN MASS SPECTROMETRY
	2012-08-30
卷号	26 期号:16 页码:1803-1809
ISSN号	0951-4198
DOI	10.1002/rcm.6295
英文摘要	RATIONALE Recently, human telomeric DNA was found to be transcribed into RNA transcripts composing of tandem repeats of r(UUAGGG) which can form G-quadruplex structures. Studies have shown that human telomeric RNA is associated with the telomerase activity in vitro. Finding high affinity small molecule ligands binding to the telomeric RNA G-quadruplex may facilitate the regulation of the telomerase activity. METHODS The 12-mer and 24-mer telomeric RNA sequences, r(UAGGGUUAGGGU) and r(UAGGGUUAGGGUUAGGGUUAGGGU), were synthesized by TaKaRa Biotechnology (Dalian) Co., Ltd. (TaKaRa, Dalian) with high-performance liquid chromatography (HPLC) purification. Electrospray ionization ion-trap mass spectrometry was used to evaluate the binding affinities of three natural flexible cyclic molecules, tetrandrine, fangchinoline and cepharanthine, with the telomeric RNA G-quadruplexes. The fragmentation pathways of the G-quadruplexes and G-quadruplex-ligand complexes were investigated by tandem mass spectrometry. RESULTS the natural flexible cyclic molecules were found to have high binding affinities to the 12-mer and 24-mer RNA G-quadruplexes with stoichiometry of 1:1 to 3:1. Collision-induced dissociation tandem mass spectrometry shows that the G-quadruplex-ligand complexes lose neutral ammoniums first and the small molecule ligand subsequently. Besides, among the three flexible cyclic molecules, cepharanthine binds most tightly to the RNA G-quadruplexes than tetandrine and fangchinoline. CONCLUSIONS Three flexible cyclic small molecules were found to be potential telomeric RNA G-quadruplex ligands, especially cepharanthine, which has high affinity and binds most tightly to the RNA G-quadruplexes. These findings may provide further implications in the regulation of telomeric RNA and telomerase activity. Copyright (C) 2012 John Wiley & Sons, Ltd.
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000306279800010
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/48629]
专题	中国科学院化学研究所
通讯作者	Yuan, Gu
作者单位	Peking Univ, Coll Chem & Mol Engn, Key Lab Bioorgan Chem & Mol Engn, Beijing Natl Lab Mol Sci,Minist Educ,Dept Chem Bi, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Cui, Xiaojie,Lin, Sen,Zhou, Jiang,et al. Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2012,26(16):1803-1809.
APA	Cui, Xiaojie,Lin, Sen,Zhou, Jiang,&Yuan, Gu.(2012).Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,26(16),1803-1809.
MLA	Cui, Xiaojie,et al."Investigation of non-covalent interaction of natural flexible cyclic molecules with telomeric RNA G-quadruplexes by electrospray ionization mass spectrometry".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 26.16(2012):1803-1809.