Journal
DALTON TRANSACTIONS
Volume 41, Issue 38, Pages 11807-11812Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2dt31303k
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Funding
- National Natural Science Foundation of China [21121061, 20831006, 21172274]
- Guangdong Provincial Natural Science Foundation [9351027501000003]
- Ministry of Education of China [20100171110013]
- Fundamental Research Funds for the Central Universities
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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 (K-b values ranging from 10(4)-10(8) 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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