Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy.
Chemistry. 2012 Nov 5;18(45):14487-96. doi: 10.1002/chem.201202097. Epub 2012 Sep 20.
We report herein a solvent-free and microwaved-assisted synthesis of several water soluble acyclic pentaheteroaryls containing 1,2,4-oxadiazole moieties (1-7). Their binding interactions with DNA quadruplex structures were thoroughly investigated by FRET melting, fluorescent intercalator displacement assay (G4-FID) and CD spectroscopy. Among the G-quadruplexes considered, attention was focused on telomeric repeats together with the proto-oncogenic c-kit sequences and the c-myc oncogene promoter. Compound 1, and to a lesser extent 2 and 5, preferentially stabilise an antiparallel structure of the telomeric DNA motif, and exhibit an opposite binding behaviour to structurally related polyoxazole (TOxaPy), and do not bind duplex DNA. The efficiency and selectivity of the binding process was remarkably controlled by the structure of the solubilising moieties.
我们在此报告了一种无溶剂微波辅助合成几种含有 1,2,4-噁二唑部分的水溶性非环五杂芳族化合物（1-7）的方法。通过荧光共振能量转移（FRET）熔融、荧光嵌入剂置换 assay（G4-FID）和 CD 光谱法，深入研究了它们与 DNA 四链体结构的结合相互作用。在所考虑的 G-四链体中，重点关注端粒重复序列以及原癌基因 c-kit 序列和 c-myc 癌基因启动子。化合物 1，在较小程度上还有 2 和 5，优先稳定端粒 DNA 基序的反平行结构，并表现出与结构相关的聚噁唑（TOxaPy）相反的结合行为，并且不与双链 DNA 结合。结合过程的效率和选择性可通过增溶部分的结构得到显著控制。
