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2'-trifluoromethylthio-modified核糖核酸具有令人惊的基配对和结构性质

Marija Košutić¹, Lukas Jud, Cyrielle Da Veiga

¹Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck , 6020 Innsbruck, Austria.

Journal of the American Chemical Society

|April 29, 2014

概括

合成和研究了具有2'-SCF3修饰的新型化核糖核酸 (RNA). 这些修改后的RNAs显示出由于形状偏好导致的双螺旋中显著的不稳定性,影响RNA结构和功能.

科学领域:

核酸的化学合成和结构生物学.
开发用于生命科学应用的修饰RNA.

背景情况:

核糖核酸 (RNA) 的化学修饰对于开发生命科学中的功能探针至关重要.
化RNA衍生物是对RNA折叠和相互作用的NMR光谱分析的宝贵工具.

研究的目的:

为了合成2个含有Oligoribonucleotides的pyrimidine nucleoside的缩写{SCF3}.
为了全面研究这些新型修饰RNA的结构和结特性.
为了合理化2缩写{SCF3}核酸修饰的结构决定因素和基配对相关性.

主要方法:

2个缩写{SCF3} 修改过的寡核酸的化学合成.
核磁共振 (NMR) 光谱用于分析RNA折叠和构造.
用于原子分辨率结构确定修饰RNA的X射线晶体学.

主要成果:

2缩写{SCF3} 修改在单链区域表现出适度的热力学稳定性,但在双螺旋区域具有高度的不稳定性.
核磁共振研究显示,在单链2缩写{SCF3}修改RNA中,对C2缩写{'} -endo conformation有很强的偏好.
X射线结构显示,2个缩写{SCF3} 核化物采用C3缩写{'} -endo conformations在双重体中,可能是由于晶体包装,原子形成密切接触和参与结合网络.

结论:

2个核酸的内在C2 -endo conformational偏好是导致RNA双螺旋的明显不稳定.
晶体包装力可以在固态中取代固有的形状偏好.
该研究提供了SCF3修改对RNA基配对属性的结构效应的合理化.

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