9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA

Wan Jin Zhang, Tian Miao Ou, Yu Jing Lu, Ying Yu Huang, Wei Bin Wu, Zhi Shu Huang, Jin Lin Zhou, Kwok Yin Wong, Lian Quan Gu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

122 Citations (Scopus)

Abstract

The interaction of berberine and its 9-substituted derivatives with human telomeric DNA d[G3(T2AG3)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.
Original languageEnglish
Pages (from-to)5493-5501
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number16
DOIs
Publication statusPublished - 15 Aug 2007

Keywords

  • 9-Substituted berberine
  • Synthesis
  • Telomerase inhibitor
  • Telomeric G-quadruplex DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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