Modified Nucleosides as RNA Components. Structure, Biological Role and Drug Design

Abstract

More than 100 modified nucleosides with different structures and functions are known as components of nucleic acids. Carbohydrate-modified (disaccharide) nucleosides are components of tRNA and poly(ADP-ribose) and also participate as second messengers in plants and animals. Base-modified nucleosides contain methylations, acylations, hydroxylations, amino acid and hydrocarbon functionalities, cyclic structure, sulfur or selenium. These modifications are represented in various types of RNA (transport—t, ribosomal—r, matrix—m, small-interfering—si, non-coding—nc RNAs) among all domains of life. They have many important biological implications: RNA splicing, protein biosynthesis, altering RNA structure and functional organization of ribosomes. Many reviews and books were devoted to this theme, but the problems accompanied by the structural diversity of ribonucleosides and their participation in the regulation of macromolecules’ biosynthesis are updated with novel, complex data. In this chapter, general aspects of the structure and functions of modified nucleosides as minor RNA components are given in considering novel scientific achievements. This work highlights essential structural features of various general classes of naturally modified nucleosides and their biosynthetic formation and biological functions. A significant part of this work is devoted to medicinal chemistry. Here we consider the mechanism of action of synthetic nucleosides and drugs on their basis, changing properties of viral RNAs and thus leading to inhibition of viral reproduction and application of nucleoside stable isotope labeled internal standards (SILIS) for analysis of RNA probes.