Functionalized Nucleoside Analogs as Probes for Nucleic Acid Recognition and Synthons for Supramolecular Assemblies

Abstract

Nucleosides, the basic component of nucleic acids, can be functionalized at various positions of the nucleobase and sugar residue without affecting its recognition property. When carefully functionalized, such nucleoside analogs can be used as probes for studying nucleic acid structure and function or as therapeutic tool or can be used to build self-assembling systems. We have used a simple chemical modification approach to develop new families of responsive nucleoside probes and supramolecular synthons. The thesis synopsis is divided into two parts. In the first part, we describe the development of novel dual-purpose nucleobase-modified nucleoside analogs containing a fluorophore and X-ray anomalous scattering label (Se atom). The nucleoside analogs are derived by attaching selenophene at the -deoxyuridine (SedU) and uridine (SeU). The nucleosides5-position of 2 are minimally perturbing and highly sensitive to their microenvironment. Utilizing these properties, we designed biophysical assays to study the structure and ligand binding ability of the bacterial ribosomal decoding site RNA and human telomeric repeats concurrently by fluorescence and X-ray crystallography. In the second part, we discuss the development of functionalized nucleoside-fatty acid hybrids, which show hierarchical self-assembling process to form organogels and water-induced gels. In one of the designs, nucleolipid synthons are made of environment-sensitivity fluorescent nucleoside analogs as the head group, and fatty acids attached to the ribose sugar as the lipophilic group. Alternatively, nucleolipid synthons are simply prepared by attaching fatty acids to the sugar residue of native nucleosides. Depending on the modification on the nucleobase and sugar residues, the nucleolipids form gels, which are highly responsive to external stimuli (physical and chemical) and show aggregation-induced enhanced emission, or form materials whose surface, can be switched from highly hydrophobic to hydrophilic and vice versa. We expect that this simple approach of probe and supramolecular synthon design could lead to the emergence of a new family of smart materials and probes.