Burkhart Ines, Wirmer-Bartoschek Julia, Plavec Janez, Schwalbe Harald
Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe University, Max von Laue Str. 7, 60438, Frankfurt am Main, Germany.
Slovenian NMR Centre, National Institute of Chemistry, Ljubljana, SI-1000, Slovenia.
Chemistry. 2025 Jun 6;31(32):e202501377. doi: 10.1002/chem.202501377. Epub 2025 May 2.
Telomeric DNA forms G-quadruplex (G4) structures. These G4 structures are crucial for genomic stability and therapeutic targeting. Using time-resolved NMR and CD spectroscopy, we investigated how the ligand Phen-DC modulates the folding of the human telomeric repeat 23TAG DNA. The kinetics are modulated by the ligand and by the presence of potassium cations (K). Ligand binding to G4 occurs via a triphasic process with fast and slow phases. Notably, for the G4 structure in the presence of K, the slow rate is ten times slower than without K. These findings offer key insights into the modulation of the complex folding landscape of G4s by ligands, advancing our understanding of G4-ligand interactions for potential therapeutic applications.
端粒DNA形成G-四链体（G4）结构。这些G4结构对于基因组稳定性和治疗靶点至关重要。利用时间分辨核磁共振和圆二色光谱，我们研究了配体Phen-DC如何调节人类端粒重复序列23TAG DNA的折叠。动力学受到配体和钾阳离子（K）存在的调节。配体与G4的结合通过一个具有快速和慢速阶段的三相过程发生。值得注意的是，对于存在K的G4结构，慢速速率比没有K时慢十倍。这些发现为配体对G4复杂折叠态势的调节提供了关键见解，推动了我们对G4-配体相互作用在潜在治疗应用方面的理解。
