Tedeschi Tullia, Tonelli Alessandro, Sforza Stefano, Corradini Roberto, Marchelli Rosangela
Department of Organic and Industrial Chemistry; University of Parma; Parma, Italy.
Artif DNA PNA XNA. 2010 Oct;1(2):83-89. doi: 10.4161/adna.1.2.13899.
The design and the synthesis of a PNA oligomer containing a pyrenyl residue in the backbone were performed. PNA sequence was chosen complementary to a "G rich" target sequence involved in G-quadruplex formation. The pyrenyl unit replaced a nucleobase in the middle of the PNA through covalent linkage to the backbone by a carboxymethyl unit. A systematic study on the binding properties of this probe towards DNA and RNA complementary strands was carried out by UV and fluorescence spectroscopy. UV melting curves indicated that the PNA probe binds more tightly to RNA rather than to DNA. Thermodynamic data obtained by Van't Hoff fitting of the melting curves indicated that, in the case of RNA, a more favorable interaction occurs between the pyrenyl unit and the RNA nucleobases, leading to a very favorable enthalpic contribution.The fluorescence analysis showed specific quenching of the pyrene emission associated to the formation of the full-match PNA-DNA or PNA-RNA duplexes. Again, this behavior was more evident in the case of RNA, consistently with the stronger interaction of the pyrenyl unit with the complementary strand. In order to study the sequence specificity of the pyrenyl-PNA probe (pyr-PNA), recognition experiments on mismatched DNA and RNA sequences were also performed.
进行了一种在主链中含有芘基残基的肽核酸(PNA)低聚物的设计与合成。选择与参与G-四链体形成的“富含G”靶序列互补的PNA序列。芘基单元通过羧甲基单元与主链共价连接,取代了PNA中间的一个核苷酸碱基。通过紫外和荧光光谱对该探针与DNA和RNA互补链的结合特性进行了系统研究。紫外熔解曲线表明,PNA探针与RNA的结合比与DNA的结合更紧密。通过对熔解曲线进行范特霍夫拟合得到的热力学数据表明,在RNA的情况下,芘基单元与RNA核苷酸碱基之间发生了更有利的相互作用,导致了非常有利的焓贡献。荧光分析表明,与完全匹配的PNA-DNA或PNA-RNA双链体形成相关的芘发射发生了特异性猝灭。同样,这种行为在RNA的情况下更为明显,这与芘基单元与互补链的更强相互作用一致。为了研究芘基-PNA探针(pyr-PNA)的序列特异性,还对不匹配的DNA和RNA序列进行了识别实验。