9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA |
| |
Authors: | Zhang Wan-Jin Ou Tian-Miao Lu Yu-Jing Huang Ying-Yu Wu Wei-Bin Huang Zhi-Shu Zhou Jin-Lin Wong Kwok-Yin Gu Lian-Quan |
| |
Affiliation: | School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China. |
| |
Abstract: | The interaction of berberine and its 9-substituted derivatives with human telomeric DNA d[G(3)(T(2)AG(3))(3)](telo21) has been investigated via CD spectroscopy, fluorescence spectroscopy, PCR-stop assay, competitive dialysis, and telomerase repeat amplification protocol (TRAP) assay. The results indicated that these semisynthesized compounds could induce and stabilize the formation of anti-parallel G-quadruplex of telomeric DNA in the presence or absence of metal cations. Compared with berberine, the 9-substituted derivatives exhibit stronger binding affinity with G-quadruplex and higher inhibitory activity for telomerase. Introduction of a side chain with proper length of methylene and terminal amino group to the 9-position of berberine would significantly strengthen the binding affinity with G-quadruplex, resulting in increasing inhibitory effects on the amplification of telo21 DNA and on the telomerase activity. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|