Synthesis Of Chiral Peptide Nucleic Acids And Their Interaction With DNA

Peptide nucleic acid(PNA)is a kind of artificial nucleic acid with peptide backbone instead of phosphordiester deoxyribose units.Owing to its neutral backbone,PNA can bind to DNA and RNA more efficiently than natural nucleic acids,and exhibits ambitious thermal stability.In the past decades,PNA has attracted great attentions due to its high affinity to natural nucleic acids and good biocompatibility.However,the lack of chirality in forming duplex with DNA/RNA restricts its further application,either in gene therapy or in the analytical science.In recent years,scientists have made great effects on the design and synthesis of chiral peptide nucleic acids,both cyclic and acylic chiral units were incorporated into the backbone of PNA.Although great progress has been made,the oriention recognition between PNA and DNA/RNA do not meet the demand,as the chirality in these peptide nucleic acids cannot match natural DNA precisely.Therefore,it is of great importance to design a new type of highly matched chiral peptide nucleic acid.In this thesis,we incorporated the D-deoxyribose ring in natural DNA as the chiral unit into the backbone of peptide nucleic acid,to increase the oriention selectivity of PNA-DNA duplex.Based on our design,the phosphate diester bond in natural DNA was replaced with diamide unit with different structure.The binding efficiency and stability of this chiral PNA to natural DNA could be adjusted by alternating the structure of diamide unit.To achieve this,we reported the first designed a novel peptide nucleic acid monomer as the basic unit.The monomer was synthesized by utilizing commercial nucleoside via multistep organic synthetic,such as Mitsunobu reaction,S_N2 reaction,selective protection of amino groups and so on.During the synthesis,we have optimized the reaction conditions in detail,and established an efficient preparation protocol.We then prepared the peptide nucleic acid via solid phase and liquid phase synthetic methods,respectively,and studied their merits.Finally,we investigated the thermodynamatic properities of duplex and triplex formed with T3 peptide nucleic acid with natural DNA.