Design, Synthesis, Characterization,and Biological Activities Of A Novel Polyamide-Dicyclen Conjugate

Artificial nuclease can mimic the function of natural nuclease by breaking the backbone of DNA site-specifically. And these small molecules can also be used as molecular biological tools and genetic therapy agents.Polyamides containing N-methylpyrrole/imidazole have attracted considerable attention of biological chemists for their membranes permeability and have the potential to control specific gene expression. On the other hand, Some dinuclear macrocyclic polyamine metal complexes with pairs of metal ions to interact with the DNA, may have much more tight bindings than two equiv of corresponding monometallic complexes through a concerted two-point binding-to-DNA mechanism.In order to further improve the function of dicyclen-Zn2+complexes, a novel polyamide-dicyclen conjugate L1was designed, and its molecular structure had been identified perfectly by investigating its ESI-MS" fragmentation.Electrophoretic mobility shift assay showed that the compound L1had an obvious binding activity to pUC18DNA.Electrophoresis showed, without zinc (Ⅱ) ion, that the compound L1could only bind DNA minor groove and turn the Form Ⅰ to the Form Ⅱ. It was confirmed that L1has binding ability to DNA. It was obvious that L1could cleave super-helix DNA when the concentration of zinc (Ⅱ) ion in the mixture was twice as that of L1Especially, the cleavage was enhanced significantly in the condition ([L1]=1μM, pH=7.7-7.9).