Synthesis Of PNA-cyclen Compound And DNA Cleavage By Their Metal Complexes

Chemical nucleases are a new challenging field that is quickly developing in chemical biology. PNA (peptide nucleic acid) is the favorable tool in biology because of its high stability and high affinity with nucleic acid. It has wide application in gene therapy, molecular hybridization, PCR enhancement, nucleic capture and gene separation. Macrocyclic polyamine is a type of unique and excellent ligand for coordinating metal ions. Macrocyclic polyamine metal complexes as enzyme models are widely used in molecular recognition, catalyst, fluorescent probe, self-assembling. In this dissertation, we focus on creating new chemical nucleases through linking PNA and cyclen.We synthesized a novel compound which PNA monomer linked with cyclen (1,4,7,10 -tetraazacyclododecane).The catalytic activity on DNA cleavage was investigated. The results showed that copper(II) complexes can catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) under physiological conditions to produce selectively nicked DNA (Form II), the mechanism was studied. The cleavage promoted by the complex might take place by a hydrolytic pathway. We also synthesized OligoPNAs by liquid and solid phase method.