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 > 北京大学 > 化学与分子工程学院

	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	质谱学快讯
	2012
关键词	HIV-1 INTEGRASE INHIBITORS DIMERIC G-QUADRUPLEXES REPEAT-CONTAINING RNA DNA RECOGNITION COMPLEXES BINDING PROMOTER LIGANDS
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.; Biochemical Research Methods; Chemistry, Analytical; Spectroscopy; SCI(E); PubMed; 4; ARTICLE; 16; 1803-1809; 26
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/149856]
专题	化学与分子工程学院
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]. 质谱学快讯,2012.
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.质谱学快讯.
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".质谱学快讯 (2012).