Preparation And Biological Activities Of Polyaspartic Acid Derivatives Modified By Macrocyclic Polyamine

Artificial nuclease can mimic the function of natural nuclease by breaking the backbone of DNA site-specifically. And these molecules can also be used as molecular biological tools and genetic therapy agents. At present, the researches about artificial nuclease are usually limited in metallnuclease and comparing with the success of metallnuclease, metal-free ones are seldom reported and their effect in DNA cleavage is not remarkable.In particular, PASP has attracted much attention because of its favorable biological properties such as nontoxicity, biocompatibility and biodegradability. The nitrogen-atoms of the ring in macrocyclic polyamine were apt to proton, so they can form complex with DNA due to electrostatic interaction. In addition, they can recognize DNA particularity and their ligands with metal ion have been widely studied as efficient nuclease.We prepared three novel compounds, PASP-tacn, PASP-cyclen and PASP-cyclam, via grafting1-(4-aminobutyl) macrocyclic polyamines onto PASP skeleton, and they have been characterized by IR,1H NMR,13C NMR, TGA, GPC and Maldi-Tof. In certain conditions, these novel compounds can bind DNA and the binding results are decided by their structure, graft degree and operational time. However, they can not be treated as good gene delivery.Surprisingly, we found PASP-tacn, PASP-cyclen and PASP-cyclam, they all have excellent ability of DNA cleavage, expecially on scission of double-strand DNA. It is infrequent that they can efficiently catalyze double-strand with unprecedented reactivity, while without adding any metal ions, and even linearize double-strand DNA completely. More detailed studies on these graft polymers will be helpful to the nature of the design of highly efficient artificial nucleases.