Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku Kyoto 606-8502, Japan.
J Am Chem Soc. 2010 Mar 24;132(11):3778-82. doi: 10.1021/ja908897j.
In addition to the Watson-Crick double helix, secondary DNA structures are thought to play important roles in a variety of biological processes. One important example is the G-quadruplex structure that is formed at the chromosome ends, which inhibits telomerase activity by blocking its access to telomeres. G-quadruplex structures represent a new class of molecular targets for DNA-interactive compounds that may be useful to target telomeres. Here, we reported the first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene. We propose a new ligand-binding cleft between two telomeric human G-quadruplexes linked by a TTA linker. We found that the cyclic helicene M1 exhibited potent inhibitory activity against telomerase.
除了沃森-克里克双螺旋外，人们认为二级 DNA 结构在多种生物过程中发挥着重要作用。一个重要的例子是在染色体末端形成的 G-四链体结构，它通过阻止端粒酶进入端粒来抑制端粒酶的活性。G-四链体结构代表了一类新的分子靶点，用于与 DNA 相互作用的化合物，这些化合物可能有助于靶向端粒。在这里，我们报道了手性环状螺旋烯对四链 DNA 进行对映选择性识别的第一个例子。我们提出了一个新的配体结合裂隙，连接两个通过 TTA 接头连接的端粒人 G-四链体。我们发现，环状螺旋烯 M1 对端粒酶表现出很强的抑制活性。
