Department of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, USA.
J Am Chem Soc. 2010 Jun 30;132(25):8676-81. doi: 10.1021/ja101384k.
The important role that noncoding RNA plays in cell biology makes it an attractive target for molecular recognition. However, the discovery of small molecules that bind double helical RNA selectively and may serve as biochemical probes and potential drug leads has been relatively slow. Herein, we show that peptide nucleic acids, as short as six nucleobases, bind very strongly (K(a) > 10(7)) and sequence selectively to a homopurine tract of double helical RNA at pH 5.5. The isothermal titration calorimetry and circular dichroism experiments suggest that the binding mode may be a sequence selective triple helix formation. Our results have implications for development of biochemical probes to study function of noncoding RNAs and design of compounds with potential antibacterial and antiviral activity.
非编码 RNA 在细胞生物学中发挥着重要作用，使其成为分子识别的一个有吸引力的靶点。然而，发现能够选择性结合双链 RNA 的小分子，并作为生化探针和潜在的药物先导物的进展相对缓慢。在此，我们表明，短至 6 个碱基的肽核酸在 pH 5.5 时非常强（K(a) > 10(7))和序列选择性地结合双链 RNA 的同聚嘌呤链。等温滴定量热法和圆二色性实验表明，结合模式可能是序列选择性的三螺旋形成。我们的结果对开发生化探针以研究非编码 RNA 的功能和设计具有抗菌和抗病毒活性的化合物具有重要意义。
