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MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China
; Fax: +86 2084112245
; Tel: +86 2084113788
Dalton Trans., 2012,41, 11807-11812
18 Jun 2012,
31 Jul 2012
First published online
02 Aug 2012
A series of four self-assembled Pt(II) molecular squares with 4,4′-dipyridyl or pyrazine bridges, including the previously reported Pt(II) squares [Pt(en)(4,4′-dipyridyl)]4(NO3)8 (1), were investigated for their abilities to act as selective and effective human telomeric (htelo) G-quadruplex binders. FRET and SPR studies demonstrated that Pt(II) squares could discriminate against duplex DNA, and show promising selectivity between intramolecular G-quadruplexes. PCR-stop assays and CD studies showed that Pt(II) squares strongly induced the formation of parallel G-quadruplexes. ITC experiments indicated that Pt(II) squares could bind to the G-quadruplex with high binding constants (Kb values ranging from 104–108 M−1). All four Pt(II) squares were effective inhibitors of human telomerase, and showed anticancer efficacy. This was particularly the case for [Pt(NH3)2(4,4′-dipyridyl)]4(NO3)8 (2), which exhibited a 15-fold higher antiproliferative effect on A549/cisR cells than cisplatin.
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