Czech Academy of Sciences, Institute of Biophysics, Kralovopolska 135, Brno CZ-61265, Czech Republic.
Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284-2006, United States.
Inorg Chem. 2020 Oct 19;59(20):15135-15143. doi: 10.1021/acs.inorgchem.0c02070. Epub 2020 Sep 29.
RNA triplexes are significant tertiary structure motifs that are found in many functional RNAs. Hence, small molecules capable of recognition, binding, and stabilization of the triple-helical RNA structures are emerging as attractive potential molecular biology tools and therapeutic agents. Here, we utilize methods of molecular biology and biophysics to study the interactions of a series of antitumor substitution-inert polynuclear platinum complexes (SI-PPCs) with triple-helical RNA structures. We show that SI-PPCs recognize and stabilize RNA triplexes and inhibit reverse transcription preferentially in the RNA template prone to the triplex formation. These so far unexplored properties of SI-PPCs suggest that the targeting of triple-stranded regions in RNA might contribute to the biological effects of SI-PPCs.
RNA 三链体是许多功能 RNA 中存在的重要三级结构基序。因此,能够识别、结合和稳定三螺旋 RNA 结构的小分子正成为有吸引力的潜在分子生物学工具和治疗剂。在这里,我们利用分子生物学和生物物理学的方法来研究一系列抗肿瘤取代惰性多核铂配合物(SI-PPCs)与三螺旋 RNA 结构的相互作用。我们表明,SI-PPCs 识别和稳定 RNA 三链体,并优先抑制 RNA 模板中易于形成三链体的逆转录。这些迄今为止尚未被探索的 SI-PPCs 的特性表明,靶向 RNA 中的三链区域可能有助于 SI-PPCs 的生物学效应。