Synthesis And Application Of Nucleic Acid Modification Reagents

Nucleic acid modifying agents are a class of compounds that have broad application prospects.They can modify the bases,glycosides and other functional group of nucleic acid molecules,and change function and stability of the nucleic acid molecules to exert biological activity;Or by covalent modification,they can label nucleic acid molecules that have important biological functions in chemical biology studies as an important chemical tool.In this thesis,we synthesized two kinds of modified nucleic acid reagents and study the properties of them,and the we had attempts at chemical biology applications.The first part of this thesis is mainly about the synthesis of four spiropyran SPI-SPIV and study of their photochromic reaction?reaction with dA?dG.We used UV light to induce its ring-opening reaction to promote them spontaneously generated highly reactive intermediates QMs,then nucleophilic sites of DNA could have alkylation reaction with them;under visible light or dark conditions,they can generate irreversible ring closure products,thereby modifying the nucleic acids.We found that,SPI and SPII molecules can not form ring-opening structure through UV-inducing,and can not form quinone methides intermediate;and SP? can not form ring-opening structure through UV-inducing,but-OAc is not a good leaving group,it can not form quinone methides intermediate molecule,SP? has good response to UV irradiation,and formed QMs structure,and thus capable of reacting with dA,but the drawback is that the chloro group is too lively,it produces QMs intermediate so fast,the rate of reaction with water is faster than the reaction with dA,leading to a lower yield of the reaction and dA.Next we will further change the substituents on the 6 position and the leaving group on 8 position,in order to synthesize a reactive compound.The second part of this thesis is mainly about the synthesis of 3-(but-3-yn-1-y1)-3-(2-iodoethyl)-3H-diazirine,and we try to use the compound to functionally modify microRNA.We successfully obtained this compound,and found that it can react with primary amines benzylamine by experiments;However,under a variety of conditions,we tried to use this molecule to modify the amino-modified double-stranded RNA on the 5 'end,but failed.For the next,we would try to synthesize a new compound that has an activated ester group,and we will try to change the reaction conditions.