Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by small-molecule natural products | |
Cui, Xiaojie; Lin, Sen; Yuan, Gu | |
刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES |
2012-05-01 | |
卷号 | 50期号:4页码:996-1001 |
关键词 | G-quadruplex C-kit Oncogene Esi-ms Cd Small Molecules Autodock3 |
ISSN号 | 0141-8130 |
DOI | 10.1016/j.ijbiomac.2012.02.029 |
文献子类 | Article |
英文摘要 | The c-kit oncogene plays important roles in cell growth and proliferation which is associated with many human tumors. In this study, electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to evaluate the formation and recognition of the G-quadruplex by d(AGGGAGGGCGCTGGGAGGAGGG) in the promoter region of the c-kit oncogene. Among the twelve small natural molecules studied, three crescent-shaped small molecules (chelerythrine, jatrorrhizine and berberine, named as P1-P3) and one flexible cyclic small molecule (fangchinoline, named as P4) were found to bind to the G-quadruplex with high affinities. The melting experiments demonstrate that P1-P4 can significantly enhance the stability of the G-quadruplex with the ordering of P1 approximate to P4> P3> P2. Further insight into the binding mode of small molecules with the G-quadruplex by Autodock3 analysis reveals that P1-P3 prefer the end-stacking mode with the G-quadruplex through pi-pi interaction and P4 prefers to insert into the groove outside the G-tetrads. Thus, our research finds that four ligands (P1-P4) from small natural molecules have high affinity to, and can significantly enhance the stability of the G-quadruplex in the promoter region of the c-kit oncogene. (C) 2012 Elsevier B.V. All rights reserved. |
WOS关键词 | IONIZATION MASS-SPECTROMETRY ; GASTROINTESTINAL STROMAL TUMORS ; TYROSINE KINASE ; BINDING ; REGION ; GENE ; DNA ; STABILIZATION ; MUTATIONS ; COMPLEXES |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
出版者 | ELSEVIER SCIENCE BV |
WOS记录号 | WOS:000304230000017 |
内容类型 | 期刊论文 |
源URL | [http://cas-ir.dicp.ac.cn/handle/321008/167288] |
专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
通讯作者 | Yuan, Gu |
作者单位 | Peking Univ, Beijing Natl Lab Mol Sci, Key Lab Bioorgan Chem & Mol Engn, Coll Chem & Mol Engn,Dept Chem Biol,Minist Educ, Beijing 100871, Peoples R China |
推荐引用方式 GB/T 7714 | Cui, Xiaojie,Lin, Sen,Yuan, Gu. Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by small-molecule natural products[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2012,50(4):996-1001. |
APA | Cui, Xiaojie,Lin, Sen,&Yuan, Gu.(2012).Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by small-molecule natural products.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,50(4),996-1001. |
MLA | Cui, Xiaojie,et al."Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by small-molecule natural products".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 50.4(2012):996-1001. |
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