Mechanism of acridine-based telomerase inhibition and telomere shortening

Gunaratnam, M., Greciano, O., Martins, C., Reszka, A.P., Schultes, C.M., Morjani, H., Riou, Jean-Francois and Neidle, S. (2007) Mechanism of acridine-based telomerase inhibition and telomere shortening. Biochemical Pharmacology, 74 (5). pp. 679-689. 10.1016/j.bcp.2007.06.011.

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DOI: 10.1016/j.bcp.2007.06.011


The trisubstituted acridine compound BRACO-19 has been developed as a ligand for stabilising G-quadruplex structures. It is shown here that BRACO-19 produces short- and long-term growth arrest in cancer cell lines, and is significantly less potent in a normal cell line. BRACO-19 reduces telomerase activity and long-term telomere length attrition is observed. It is also shown that BRACO-19 binds to telomeric single-stranded overhang DNA, consistent with quadruplex formation, and the single-stranded protein hPOT1 has been shown to be displaced from the overhang in vitro and in cellular experiments. It is concluded that the cellular activity of BRACO-19 can be ascribed both to the uncapping of 3′ telomere ends and to telomere shortening that may preferentially affect cells with short telomeres

Item Type:Article
Uncontrolled Keywords:G-quadruplex ligands; Telomerase; Telomere targeting
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2741
Journal or Publication Title:Biochemical Pharmacology
Deposited By:Library Staff
Deposited On:20 Jan 2012 15:13
Last Modified:20 Jan 2012 15:13

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