Honisch Claudia, Ragazzi Eugenio, Hussain Rohanah, Brazier John, Siligardi Giuliano, Ruzza Paolo
Institute of Biomolecular Chemistry of CNR, Via F. Marzolo, 1, 35131 Padova, Italy.
Department of Chemical Sciences, University of Padua, Via F. Marzolo, 1, 35131 Padova, Italy.
Pharmaceutics. 2021 Jul 21;13(8):1104. doi: 10.3390/pharmaceutics13081104.
G-quadruplex (G4) forming DNA sequences were recently found to play a crucial role in the regulation of genomic processes such as replication, transcription and translation, also related to serious diseases. Therefore, systems capable of controlling DNA and RNA G-quadruplex structures would be useful for the modulation of various cellular events. In particular, peptides represent good candidates for targeting G-quadruplex structures, since they are easily tailored to enhance their functionality. In this work, we analyzed, by circular dichroism and synchrotron radiation circular dichroism spectroscopies, the interaction of a 25-residue peptide deriving from RHAU helicases () with three G-quadruplex-forming oligonucleotide sequences, in both sodium- and potassium-containing buffers, the most relevant monovalent cations in physiological conditions. The peptide displayed greater affinity for the G4 sequences adopting a parallel structure. However, it showed the ability to also interact with antiparallel or hybrid G-quadruplex structures, inducing a conformation conversion to the parallel structure. The stability of the oligonucleotide structure alone or in presence of the peptide was studied by temperature melting and UV denaturation experiments, and the data showed that the interaction with the peptide stabilized the conformation of oligonucleotide sequences when subjected to stress conditions.
最近发现，能形成G-四链体（G4）的DNA序列在复制、转录和翻译等基因组过程的调控中起着关键作用，这些过程也与严重疾病相关。因此，能够控制DNA和RNA G-四链体结构的系统将有助于调节各种细胞事件。特别是，肽是靶向G-四链体结构的良好候选物，因为它们易于定制以增强其功能。在这项工作中，我们通过圆二色光谱和同步辐射圆二色光谱，分析了源自RHAU解旋酶的一个25个残基的肽与三个形成G-四链体的寡核苷酸序列在含钠和含钾缓冲液中的相互作用，这两种缓冲液是生理条件下最相关的单价阳离子。该肽对采用平行结构的G4序列表现出更高的亲和力。然而，它也显示出与反平行或杂合G-四链体结构相互作用的能力，诱导其构象转变为平行结构。通过温度熔解和紫外变性实验研究了寡核苷酸结构单独存在或在该肽存在时的稳定性，数据表明，在应激条件下，与该肽的相互作用稳定了寡核苷酸序列的构象。
