Identification of a New G-Quadruplex Motif in the KRAS Promoter and Design of Pyrene-Modified G4-Decoys with Antiproliferative Activity in Pancreatic Cancer Cells
Identification of a New G-Quadruplex Motif in the KRAS Promoter and Design of Pyrene-Modified G4-Decoys with Antiproliferative Activity in Pancreatic Cancer Cells
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DOI：
10.1021/jm800874t
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发表时间：
2009-01-22
影响因子：
7.3
通讯作者：
Xodo, Luigi E.
中科院分区：
文献类型：
--
作者：
Cogoi, Susanna;Paramasivam, Manikandan;Xodo, Luigi E.
位于人类 KRAS 基因启动子、核酸酶超敏元件 (NHE) 内的新四链体基序已得到表征。人们发现模仿这种四链体的寡核苷酸会与 NHE 和胰腺癌细胞核提取物之间的 DNA-蛋白质复合物竞争。当用 (R)-1-O-[4-1-(1-芘基乙炔基) 苯基甲基]甘油插入 (TINA) 进行修饰时，四链体寡核苷酸在 Panc-1 细胞中表现出 T-m 的显着增加（Delta T-m 从 22 到 32 摄氏度）和强大的抗增殖作用。
A new quadruplex motif located in the promoter of the human KRAS gene, within a nuclease hypersensitive element (NHE), has been characterized. Oligonucleotides mimicking this quadruplex are found to compete with a DNA-protein complex between NHE and a nuclear extract from pancreatic cancer cells. When modified with (R)-1-O-[4-1-(1-pyrenylethynyl) phenylmethyl]glycerol insertions (TINA), the quadruplex oligonucleotides showed a dramatic increase of the T-m (Delta T-m from 22 to 32 degrees C) and a strong antiproliferative effects in Panc-1 cells.