Interaction of an acridine dimer with DNA quadruplex structures
Interaction of an acridine dimer with DNA quadruplex structures
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DOI：
10.1080/07391102.2001.10506758
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Mergny, JL
中科院分区：
文献类型：
--
作者：
Alberti, P;Ren, JS;Mergny, JL
大多数癌细胞中端粒酶活性的重新激活支持了端粒酶是肿瘤相关靶点的概念，端粒酶抑制剂已被提出为新的潜在抗癌药物。端粒富含G的单链DNA在体外可以采用分子内G-四链结构，这已被证明具有抑制端粒酶活性的作用。富C序列也可以采用四链(插层)结构(I-DNA)。在染料浓度为1um时，两个吖啶类化合物均能提高G-四链体和C-四链体的熔融温度。G-四链体Tm值的增加与体外端粒酶抑制有关。在标准的TRAP试验中，最有效的化合物“Bisa”的IC50值为0.75微米。
The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt an intramolecular G-quadruplex structure in vitro, which has been shown to inhibit telomerase activity. The C-rich sequence can also adopt a quadruplex (intercalated) structure (i-DNA). Two acridine derivatives were shown to increase the melting temperature of the G-quadruplex and the C-quadruplex at 1 muM dye concentration. The increase in Tm value of the G-quadruplex was associated with telomerase inhibition in vitro. The most active compound, "BisA", showed an IC50 value of 0.75 muM in a standard TRAP assay.