Pt(II) squares as selective and effective human telomeric G-quadruplex binders and potential cancer therapeutics.
Pt(II) squares as selective and effective human telomeric G-quadruplex binders and potential cancer therapeutics.
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DOI：
10.1039/c2dt31303k
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发表时间：
2012-09
影响因子：
4
通讯作者：
Xiao-Hui Zheng;Y. Zhong;Cai-Ping Tan;L. Ji;Z. Mao
中科院分区：
文献类型：
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作者：
Xiao-Hui Zheng;Y. Zhong;Cai-Ping Tan;L. Ji;Z. Mao
研究了一系列具有 4,4'-联吡啶基或吡嗪桥的四种自组装 Pt(II) 分子方块，包括先前报道的 Pt(II) 方块 [Pt(en)(4,4'-联吡啶)](4)(NO(3))(8) (1)，研究它们作为选择性和有效的人类端粒 (htelo) G-四联体结合剂的能力。 FRET 和 SPR 研究表明，Pt(II) 方块可以区分双链体 DNA，并在分子内 G-四链体之间显示出有希望的选择性。 PCR 终止测定和 CD 研究表明，Pt(II) 方块强烈诱导平行 G-四链体的形成。 ITC 实验表明，Pt(II) 方块可以以高结合常数（K(b) 值范围为 10(4)-10(8) M(-1)）与 G-四链体结合。所有四种 Pt(II) 方块都是人端粒酶的有效抑制剂，并显示出抗癌功效。 [Pt(NH(3))(2)(4,4'-联吡啶基)](4)(NO(3))(8) (2) 的情况尤其如此，其对 A549/cisR 细胞的抗增殖作用比顺铂高 15 倍。
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.