Chemical modifications of nucleobases in functional nucleic acids / 国际药学研究杂志

ABSTRACT

The diversity of functional nucleic acids is being explored from nature and in vitro selections, including ribozyme catalysis, aptamer binding to target molecules with high specific and affinity, and RNA interference and modulation of gene expression. The great potential of chemical and biological activity of four nucleobases and the sugar-phosphate backbone in various specific tertiary structures is beyond our present imagination, and more functions remain to be found. Therefore, developing insight into the structural basis of these functional nucleic acids is invaluable in understanding their mechanisms and exploring the applications. With a special focus on the four nucleobases, we learnt that nucleobases could contribute to the functions by base stacking, electrostatic interactions, complexion with metal ions, hydrogen bonding, and even act as general acid-base in specific functions. Deletion and substitution of each nucleobases demonstrated the conservation of all the natural and unnatural functional nucleic acids. But from the success of chemical modifications at the level of functional groups on 10-23 DNAzyme, there is still room for the optimization of functional nucleic acids, for practical applications as research tools and genetic therapeutics. It is a big challenge for any functional nucleic acids, to conduct the chemical modification in a right way in the complex tertiary structures, including which residue could be used for chemical modification and which functional groups could be introduced for an expected positive effect.