The Synthesis Of PNA And PNA-Based Chiral Hybrid Catalyst Ligand

Peptide nucleic acid (PNA) is an oligonucleotide mimetics connected by peptide bonds. The specific binding between PNA and DNA or RNA fragment follows the Watson-Crick principles and is stronger than nucleic acid itself. Because PNA has skeleton structure similar to the peptide bond of polypeptide and the phosphodiester bond of nucleic acid, it not only hardly degradated by ribozymes or proteasomal, but also can be modified with other active groups at the oligo N or C terminal to achieve its functional application.Synthesis of PNA monomer is difficult and the work is the base of obtaining PNA oligomer chain, so the research of synthesis of PNA monomer is of great significance to synthesize the PNA oligomer chain and open the PNA application market.The core object in designing and developing new type ofasymmetric catalysts, which has been pursued persistently for a long time, is toachieve the high efficiency and high selectivity in the process of green catalysis.By means of combining transition metals with biomacromolecules such as DNA to take advantageof their chiral structure, there is a wide range of attention in the research ofasymmetric catalysts. We combounded PNA, which can be specifically bound to bases of DNA with high affinity, with ligands to build up a novel kind of DNA-based hybrid catalyst by means of covalent anchor.In this paper, we have prepared the PNA monomers of thymine (T), cytosine (C), and adenine (A) by fourteen steps reactions, and then prepare their carboxylic acid derivatives by two steps using the monomers as starting materials. The solution-based and solid-based synthesis conditions of the PNA monomers condensation were also explored. The synthsis route of the PNA monomer of guanine (G) was choose after the attempt of nine synthesis routes. PNA was firstly desingned to be a novel DNA-based hybrid catalyst. A novel ligand—PNAs(TTTT)-dmbipy was designed.4-methyl-4’-bromide methyl-2,2’-bipyridine was synthesized through three step reactions and created the condition of the conjugation of bipyridine and T-PNA monomer. The final product is planed to prepare by the condensation of PNA monomers. The new ligand can be complexed with DNA by covalent anchoring, and then formed the novel DNA-based hybrid catalyst with Cu2+.