Kosbar Tamer R, Sofan Mamdouh A, Abou-Zeid Laila, Pedersen Erik B
Nucleic Acid Center, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Org Biomol Chem. 2015 May 14;13(18):5115-21. doi: 10.1039/c5ob00535c.
G-rich anti-parallel DNA triplexes were modified with LNA or α-L-LNA in their Watson-Crick and TFO strands. The triplexes were formed by targeting a pyrimidine strand to a putative hairpin formed by Hoogsteen base pairing in order to use the UV melting method to evaluate the stability of the triplexes. Their thermal stability was reduced when the TFO strand was modified with LNA or α-L-LNA. The same trend was observed when the TFO strand and the purine Watson-Crick strand both were modified with LNA. When all triad components were modified with α-L-LNA and LNA in the middle of the triplex, the thermal melting was increased. When the pyrimidine sequence was modified with a single insertion of LNA or α-L-LNA the ΔTm increased. Moreover, increasing the number of α-L-LNA in the pyrimidine target sequence to six insertions, leads to a high increase in the thermal stability. The conformational S-type structure of α-L-LNA in anti-parallel triplexes is preferable for triplex stability.
富含鸟嘌呤的反平行DNA三链体在其沃森-克里克链和TFO链中用锁核酸(LNA)或α-L-LNA进行了修饰。通过将嘧啶链靶向由Hoogsteen碱基配对形成的假定发夹来形成三链体,以便使用紫外熔解方法评估三链体的稳定性。当TFO链用LNA或α-L-LNA修饰时,它们的热稳定性降低。当TFO链和嘌呤沃森-克里克链都用LNA修饰时,观察到相同的趋势。当三联体的所有三个组成部分在三链体中间用α-L-LNA和LNA修饰时,热熔解增加。当嘧啶序列用单个LNA或α-L-LNA插入进行修饰时,ΔTm增加。此外,将嘧啶靶序列中α-L-LNA的数量增加到六个插入,会导致热稳定性大幅提高。反平行三链体中α-L-LNA的构象S型结构对于三链体稳定性更有利。