Synthesis Of Hydroxyl-bearing Nucleoside Analogues And Their Effect On The Properties Of DNA

Nucleic acids have been explored for new functions extensively, such as DNA as building blocks in molecular assembly forming particular devices in nanometer scale, RNA libraries for new artifical ribozymes and aptazmers. Various chemical modification on DNA/RNA were only used for optimization of its biochemical and biophysical properties, but much less attention was paid for functionalization of DNA for selection of new functions.The structure-activity relationship of protein enzymes indicated the importance of functional groups. Hydroxyl group takes part in enzymatic hydrolysis of serine proteinases because of its strong nucleophilic property and hydrogen bonding capability. It is also the only structural difference between DNA and RNA, which endows RNA with enzymatic property and RNAi modulating gene expression and functions.In this thesis, hydroxyl groups with propynyl, (Z)-propenyl, and propyl links were introduced to DNA molecules by modification of8-aza-7-deaza-2'-deoxyadenosine. With tert-butyldiphenylsilyl group as the protecting group of nucleobase-bearing hydroxyl groups, the orthodoxy protection strategy between the hydroxyl groups was realized. Here 4 phosphoramidites and 6 oligonucleotides were synthesized. The hydroxyl-bearing phosphoramidites were successfully used in DNA solid-phase synthesis with high coupling yields. From T_m values of the modified dsDNA, the stability of DNA duplexes was little influenced when 8-aza-7-deaza-2'-deoxyadenosine replaced 2'-deoxyadenosine in dsDNAs. And hydroxypropynyl contributes to the thermal stability of dsDNA because its planar link increases the base pair stacking ability, without significant influence on the whole conformation of the B-dsDNAs compared to the unmodified counterpart, based on the observation of their CD spectra. This study offered a basis for hydroxylation of DNA for the purpose of finding new functions of DNA.