通过Pyrene-modified Guanine Tract恢复氧化G-四重复的形成和功能
Shuntaro Takahashi, Ki Tae Kim1, Peter Podbevšek2
1Department of Chemistry, Division of Advanced Materials Science , Pohang University of Science and Technology (POSTECH) , Pohang 37673 , Republic of Korea.
Journal of the American Chemical Society
|April 3, 2018
概括
在G-四重复 (G4) 结构中对瓜的氧化DNA损伤可以促进癌症. 一种新的基改性寡核酸恢复了G4功能,显示了癌症治疗的潜力.
科学领域:
- 分子生物学
- 化学生物学
- 遗传学
背景情况:
- 氧化通常会损害DNA,尤其是瓜基.
- 在G四重复 (G4) 结构中的关氨酸基容易氧化,形成8-oxo-7,8-dihydroguanine (8-oxoG).
- 氧化G4s可能会破坏基因调节并导致癌症的进展.
研究的目的:
- 研究8-oxoG在G4形成和功能上的影响.
- 开发一种恢复氧化G4s功能的化学策略.
主要方法:
- 从人体血管内皮生长因子 (VEGF) 基因促进物合成并表征了含有8-oxoG的G4结构.
- 评估氧化VEGF G4的拓差异和功能后果 (复制停滞,核结合).
- 开发并测试了一种经过激素修饰的寡核酸,以取代氧化关氨酸并恢复G4功能.
主要成果:
- 与未氧化G4相比,含有8-oxoG的VEGF G4表现出改变的拓.
- 氧化VEGF G4未能阻断复制,也没有被核素稳定.
- 经过pyrene修饰的寡核酸成功恢复了氧化G4的复制停滞和核稳定.
结论:
- 氧化的G4s表现出生物功能受损.
- 一种经过pyrene修饰的寡核酸策略可以有效地恢复氧化G4s的功能.
- 这种方法有望开发针对G4结构的新型癌症疗法.
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