Chemical Modifications On Oligonucleotides Based On The Active Sites Of Serine Proteases

Along with advancements of the technology related to nucleic acids, DNA could be doomed to an excellent self-assembling molecule owing to the particular physical and chemical properties of precise molecular recognition and exact assembly. Through chemical modifications on oligonucleotides, more functions of DNA had been exploited.Though the biology actions differed in thousands ways, protein enzymes possessed the same primary structure of polyamide. Diversities of enzymes functions were decided by the different side chains of the key amino acids, so the groups of side chains made important sense to the biology procedure of enzyme. As the members of the serine protease family, acetylcholinesterase, α-chymotrypsin and subtilisin had the similar structural character in active sites. All of them had the catalytic triad composed of serine, histidine and asparagine(or glutamic acid). It could be considered that the fine structure, which was formed by hydroxy, imidazolyl, and carboxyl provided by serine, histidine and asparagine(or glutamic acid) respectively, played the crucial role in the catalysis. Hereby, the side groups of hydroxy, imidazolyl, and carboxyl extracted from the active sites could be arrayed as the functional domain of artifical enzyme imitating the serine proteases.For such a kind of enzyme mimicking in DNA motifs, the functionalized DNA building blocks would be synthesized firstly. In this thesis, 14 modified phosphoramidites were synthesized, in which the phosphite moiety was substituted with alkyl or alkoxyl instead of non-bridged oxygen atom, and the corresponding protection strategies developed deliberately. 10 model oligonucleotides, (dT)₅ , containing modified residues mentioned above were synthesized with solid-phase synthesis protocol. Then, the deprotection strategies and a practical methodology for modified oligonucleotide...