The Open UniversitySkip to content

Antitumor Polycyclic Acridines. Part 16. Triplex DNA as a Target for DNA-Binding Polycyclic Acridine Derivatives

Missailidis, Sotiris; Modi, Chetna; Trapani, Valentina; Laughton, Charles A. and Stevens, Malcolm F.G. (2005). Antitumor Polycyclic Acridines. Part 16. Triplex DNA as a Target for DNA-Binding Polycyclic Acridine Derivatives. Oncology Research incorporating Anticancer Drug Design, 15(2) pp. 95–105.

Google Scholar: Look up in Google Scholar


Triple-stranded DNA structures have been implicated in a number of major biological processes, including the transcription and translation of a number of genes, as well as in the interaction of DNA with a number of proteins. Furthermore, antigene therapies under development are based on the recognition and binding of a single oligonucleotide strand to a double-stranded sequence, thus forming a triple helix. Triplex DNA formation is a relatively weak and temporary phenomenon; therefore, molecules that selectively bind to and stabilize triple helices may show a variety of novel biological effects. The biophysical and biological characterization of a series of antitumor polycyclic acridines that bind to triplex DNA is reported. These compounds, whose synthesis has been previously reported, have been tested for their interaction with both purine and pyrimidine type triple helices and compared with the relevant double-stranded DNA. As a pyrimidine triplex model we have used the T*AT sequence, which we have compared with the AT duplex, whereas the purine triplex oligonucleotide d[G(3)A(4)G(3)]*d[G(3)A(4)G(3)].d[C3T4C3] has been compared with the duplex d[G(3)A(4)G(3)].d[C3T4C3]. The compounds demonstrate various degrees of preferential binding to triplex DNA over normal duplex DNA, as measured by UV, fluorescence, circular dichroism, and thermal denaturation. Tri-substituted acridine derivatives demonstrated the highest affinity and ability to stabilize triplex DNA structures. Furthermore, structure/affinity analysis gives insights into the structural features that optimize affinity and selectivity for triplex DNA, and may play a role in their profile of antitumor activity.

Item Type: Journal Item
ISSN: 0965-0407
Extra Information: Some of the symbols may not have transferred correctly into this bibliographic record and/or abstract.
Keywords: polycyclic acridine derivatives; DNA binding; triplex DNA; spectrophotometric analysis; UV; fluorescence; circular dichroism; thermal denaturation; intercalating agents; anti-tumour; anti-tumor
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 3937
Depositing User: Sotiris Missailidis
Date Deposited: 03 Jul 2006
Last Modified: 19 Dec 2017 09:37
Share this page:

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU