Fabrication Of DNA-Macromolecule And DNA-Organic Molecule Block Copolymer

Atom transfer radical polymerization (ATRP) is an example of a living polymerization, the transition metal complexes as catalysts and the organic halide as initiator to initiate the unsaturated monomers to process the radical polymerization, this kind of polymerization have highly application values in the field of control synthesis of polymers. After complete the polymerization reaction, the polymer chain end with a halogen atom can be used as macromolecular initiator to the next step, to control synthesis block copolymer. By introducing a initiator with the special functional group, we can synthesis the polymer with the special functional group. Utilizing the functional group, we can combine the DNA strands with the organic macromolecular. Through the synthesis of artificial modified nucleotides, artificial nucleosides can be recognized by DNA polymerase. Then artificial nucleosides as the synthetic base will be introduced into the DNA chain, in order to realize the combination of small organic molecules with DNA.The first chapter we introduce basic knowledge of DNA block copolymer including the method to synthesis the DBCs and the self-assembly of the DBCs and the main application value of this kind of self-assembly structure. Then, we introduce the fundamental knowledge of atom transfer radical polymerization (ATRP) in detail, imcluding the system of ATRP, the mechanism of ATRP, the solvent, the monomer, the catalysis, the initiator, the application. Finaly, we introduce the basic knowledge of the nucleoside and the nucleoside analogue. And we summarize research development of the design and synthesis of 5-substituted pyrimidine nucleosides.Chapter two we discuss about a method for the synthesis of DNA block copolymer based on atom transfer radical polymerizaton. Firstly, we design and synthese a series of amphiphilic di-block copolymers with a terminal hydroxyl. The terminal hydroxyl group was introduced by the initiator. Then, we utilized the reaction between the terminal hydroxyl group and phosphorus oxychloride, the result of this reaction was that the reaction lost monomolecular hydrochloric acid and then introduced the phosophoamide into the amphiphilic di-block copolymers. Thirdly, we will utilize the phosophoamide to introduce the single or double DNA strands into the amphiphilic di-block copolymers (This procedure was finished by the DNA synthesis company). Finally, we could synthesis DNA block copolymers through this method.In cahapter three we introduce a method for the synthesis of artificial nucleotide and prove its incorporation into DNA strand by various DNA polymerases. Utilizing the emzyme’s relatively tolerance for modification at the 5-position of deoxyridine triphosphate. We designed a urdine analogue containing 2-bromoisobutyryl functionalities. Starting from commercially available 5-Indo-2’-deoxyuridine, through a five steps synthetic procedure, the target compound was successfully synthesized and charactered by 1H NMR,13C NMR,31P NMR, Elemental analysis, ESI-MS and HRMS. Furthermore the recognization of the compound by four DNA polymerases was verified by three specially designed primer extension reactions. These designed primer extension reactions could avoid the use of commmo used autoradiography techniques.