Sun Yat-Sen University, Guangzhou, People's Republic of China.
Bioorg Med Chem. 2010 Dec 1;18(23):8235-42. doi: 10.1016/j.bmc.2010.10.021. Epub 2010 Oct 28.
A series of bisaryldiketene derivatives were designed and synthesized as a new class of specific G-quadruplex ligands. The ligand-quadruplex interactions were further evaluated by FRET, ITC, and PCR stop assay. In contrast to most of the G-quadruplex ligands reported so far, which comprise an extended aromatic ring, these compounds are neither polycyclic nor macrocyclic, but have a non-aromatic and relative flexible linker between two quinoline moieties enabling the conformation of compounds to be flexible. Our results showed that these bisaryldiketene derivatives could selectively recognize G-quadruplex DNA rather than binding to duplex DNA. Moreover, they showed promising discrimination between different G-quadruplex DNA. The primary binding affinity of ligand M2 for c-myc G-quadruplex DNA was over 200 times larger than that for telomere G-quadruplex DNA.
一系列双芳基二烯酮衍生物被设计并合成，作为一类新的特定 G-四链体配体。通过荧光共振能量转移（FRET）、等温热力学滴定（ITC）和 PCR 停止实验进一步评估了配体-四链体相互作用。与迄今为止报道的大多数 G-四链体配体不同，这些化合物既不是多环的也不是大环的，而是在两个喹啉部分之间具有非芳香和相对灵活的连接体，使化合物的构象具有灵活性。我们的结果表明，这些双芳基二烯酮衍生物可以选择性地识别 G-四链体 DNA，而不是与双链 DNA 结合。此外，它们在不同的 G-四链体 DNA 之间表现出有希望的区分。配体 M2 对 c-myc G-四链体 DNA 的主要结合亲和力比端粒 G-四链体 DNA 大 200 多倍。
