期刊
JOURNAL OF CHROMATOGRAPHY A
卷 1218, 期 37, 页码 6433-6438出版社
ELSEVIER
DOI: 10.1016/j.chroma.2011.07.028
关键词
G-quadruplex ligands; High-performance liquid chromatography (HPLC); High-speed countercurrent chromatography (HSCCC); Kalopanax septemlobus (Thunb.) Koidz; Antitumor activity
资金
- National Natural Science Foundation of China [20877005, 81072576]
- Beijing Natural Science Foundation [2102016]
G-quadruplex DNA structure is considered to be a very attractive target for antitumor drug design due to its unique role in maintaining telomerase activities. Therefore, discovering ligands with high stability of G-quadruplex structure is of great interest. In this paper, high-performance liquid chromatography (HPLC) was used for fast screening of G-quadruplex ligands from the crude extract of Kalopanax septemlobus (Thunb.) Koidz, a traditional Chinese medicine. Four potent G-quadruplex ligands were firstly selected through HPLC by comparing the peak profiles and absorption intensity of the crude sample before and after interaction with G-quadruplex DNA. Then the target compounds were isolated and purified by high-speed countercurrent chromatography (HSCCC) for further confirmation of their stabilities of G-quadruplex by temperature-dependent circular dichroism (CD). Four compounds were isolated and identified as 2,4-dihydroxybenzoic acid (I), chlorogenic acid (II), caffeic acid (III) and 5-feruloylquinic acid (IV) each by MS and NMR. Finally, compound I, II, Ill were each proved to be potent G-quadruplex ligands by decreasing the peak intensity in HPLC chromatogram after complexation with G-quadruplex, which stabilize G-quadruplex by 7 +/- 2 degrees C, 10 +/- 2 degrees C, and 3 +/- 2 degrees C respectively, based on CD analyses. However, compound IV showed no G-quadruplex stability. The decrease of peak absorption intensity in HPLC chromatogram is the most important signal to find G-quadruplex ligands. This provides a very promising strategy for fast screening G-quadruplex ligands from natural plant extracts. (C) 2011 Elsevier B.V. All rights reserved.
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