Synthesis of Macrocyclic Hexaoxazole (6OTD) Dimers, Containing Guanidine and Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4 Stabilizing Properties

Structure-activity relationship studies were carried out onmacrocyclic hexaoxazole (6OTD) dimers, whose core structure stabilizes telomeric G-quadruplexes (G4). Two new 6OTDdimers having side chain amine and guanidine functional groups were synthesized and evaluated for their stabilizing ability against a telomeric G4 DNA sequence. The results show that the 6OTD dimers interact with the DNA to form 1: 1 complexes and stabilize the antiparallel G4 structure of DNA in the presence of potassium cation. The guanidine functionalized dimer displays a potent stabilizing ability of the G4 structure, as determined by using a FRET melting assay (Delta T-m = 14 degrees C).

对大环六氧唑（6OTD）二聚体进行了构效关系研究，其核心结构可稳定端粒G - 四链体（G4）。合成了两种具有侧链胺基和胍基官能团的新型6OTD二聚体，并评估了它们对端粒G4 DNA序列的稳定能力。结果表明，6OTD二聚体与DNA相互作用形成1∶1复合物，并在钾离子存在的情况下稳定DNA的反平行G4结构。通过荧光共振能量转移熔解分析（ΔT - m = 14℃）确定，胍基官能化的二聚体对G4结构显示出强大的稳定能力。