Electrospray ionization mass spectrometric exploration of the   high-affinity binding of three natural alkaloids with the mRNA   G-quadruplex in the BCL2 5 &apos;-untranslated region

doi:10.1002/rcm.6484

CORC > 北京大学 > 化学与分子工程学院

	Electrospray ionization mass spectrometric exploration of the high-affinity binding of three natural alkaloids with the mRNA G-quadruplex in the BCL2 5 '-untranslated region
	Tan, Wei ; Yuan, Gu
刊名	质谱学快讯
	2013
关键词	CIRCULAR-DICHROISM NUCLEIC-ACIDS DNA RECOGNITION PROMOTER CONVERSION ONCOGENE
DOI	10.1002/rcm.6484
英文摘要	RATIONALE The BCL2 gene encodes an integral outer mitochondrial membrane protein (25?kDa) which regulates the apoptotic death of cells. There is a 25-nucleotide G-rich sequence in the 5'-untranslated region (5'-UTR) of the BCL2 mRNA, which can adopt a G-quadruplex structure. Small molecules which could tightly bind to this structure have a potential function in the regulation of the expression of the BCL2 mRNA. METHODS The 25-mer oligonucleotide (5'-G5CCGUG4UG3AGCUG4-3') was synthesized by TaKaRa Biotechnology Co., Ltd. (TaKaRa, Dalian) with high-performance liquid chromatography (HPLC) purification. Electrospray ionization (ESI) mass spectrometry (MS) was used to probe the binding properties of natural small molecules (P) with the mRNA G-quadruplex in the BCL2 5'-UTR (BCL2Q). Collision-induced dissociation (CID) mass spectrometry and circular dichroism (CD) spectroscopy were performed to evaluate the stabilization of the mRNA G-quadruplex and its complexes. RESULTS The results from ESI mass spectra showed that three natural alkaloids (nitidine, palmatine, and jatrorrizine) have high binding affinities to the mRNA G-quadruplex with the binding stoichiometry ranging from 1:1 to 3:1. CID mass spectrometry results revealed that the G-quadruplex-ligand complex lost bases first rather than losing the binding molecules. Increases in the Tm values of the complexes of the G-quadruplex with the natural alkaloids in the CD melting experiments demonstrated that the three small molecules can stabilize the G-quadruplex structure. CONCLUSIONS Three natural small molecules were found to have very high binding affinities to the mRNA G-quadruplex and stabilize this structure. The properties of these alkaloids revealed promising potentials to regulate the expression of the BCL2 protein from the posttranscriptional pathway. Copyright (c) 2013 John Wiley & Sons, Ltd.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000313727900008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemical Research Methods; Chemistry, Analytical; Spectroscopy; SCI(E); PubMed; 9; ARTICLE; 4; 560-564; 27
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/149807]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Tan, Wei,Yuan, Gu. Electrospray ionization mass spectrometric exploration of the high-affinity binding of three natural alkaloids with the mRNA G-quadruplex in the BCL2 5 '-untranslated region[J]. 质谱学快讯,2013.
APA	Tan, Wei,&Yuan, Gu.(2013).Electrospray ionization mass spectrometric exploration of the high-affinity binding of three natural alkaloids with the mRNA G-quadruplex in the BCL2 5 '-untranslated region.质谱学快讯.
MLA	Tan, Wei,et al."Electrospray ionization mass spectrometric exploration of the high-affinity binding of three natural alkaloids with the mRNA G-quadruplex in the BCL2 5 '-untranslated region".质谱学快讯 (2013).