Pt(ii) squares as selective and effective human telomeric G-quadruplex binders and potential cancer therapeutics |
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Authors: | Xiao-Hui Zheng Yi-Fang Zhong Cai-Ping Tan Liang-Nian Ji Zong-Wan Mao |
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Institution: | MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. cesmzw@mail.sysu.edu.cn. |
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Abstract: | 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)(NO(3))(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(NH(3))(2)(4,4'-dipyridyl)](4)(NO(3))(8) (2), which exhibited a 15-fold higher antiproliferative effect on A549/cisR cells than cisplatin. |
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