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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.
MedLine Citation:
PMID:  23322663     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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'-G(5) CCGUG(4) UG(3) AGCUG(4) -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 T(m) 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 © 2013 John Wiley & Sons, Ltd.
Authors:
Wei Tan; Gu Yuan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  27     ISSN:  1097-0231     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  560-4     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 John Wiley & Sons, Ltd.
Affiliation:
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
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