9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA
| Autor: | Wei-Bin Wu, Tian-Miao Ou, Zhi-Shu Huang, Jin-Lin Zhou, Ying-Yu Huang, Wan-Jin Zhang, Kwok Yin Wong, Lian-Quan Gu, Yu-Jing Lu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Telomerase
Berberine Guanine Stereochemistry Clinical Biochemistry Fluorescence spectrometry Pharmaceutical Science Ligands G-quadruplex Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Cations Cell Line Tumor Drug Discovery Humans Molecular Biology Molecular Structure Circular Dichroism Organic Chemistry Gene Amplification DNA Telomere Ligand (biochemistry) G-Quadruplexes chemistry Metals Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 15:5493-5501 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2007.05.050 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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