Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes
Identifieur interne : 001309 ( Main/Exploration ); précédent : 001308; suivant : 001310Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes
Auteurs : Katherine J. Castor ; Johanna Mancini [Canada] ; Johanna Fakhoury ; Johanna Weill ; Johanna Kieltyka ; Johanna Englebienne ; Nicole Avakyan ; Nicole Mittermaier ; Nicole Autexier [Canada] ; Nicole Moitessier ; Nicole SleimanSource :
- [ 1860-7179 ]
Abstract
A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere‐derived intramolecular G‐quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G‐quadruplexes from sequences based on the human telomeric repeat (TTAGGG)n. The greatest stabilization was observed for the p‐chlorophenyl derivative 6 (G4DC50=0.31 μM). We also show that the G‐quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP‐LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy.
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DOI: 10.1002/cmdc.201100453
Affiliations:
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Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G‐quadruplexes from sequences based on the human telomeric repeat (TTAGGG)n. The greatest stabilization was observed for the p‐chlorophenyl derivative 6 (G4DC50=0.31 μM). We also show that the G‐quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP‐LIG assay). 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