Molecular Probe Designs For Nucleic Acid Based Detection

Nucleosides and nucleotides are powerful building units for creating functional molecules with novel properties. The structural and functional variations of these biomolecules have caused a renaissance of nucleic acid chemistry and biology, and paved the way for fresh avenues in nucleic acid research, including therapeutics, nucleic acid biology, structure-function studies, catalytic and mechanistic analysis, and material science and nanotechnology. Modified nucleic acids are instrumental in discovering functional oligonucleotides as significant biochemical and therapeutic agents. A variety of synthetic strategies have been developed to design novel analogs with tunable physico-chemical properties, such as enhanced duplex stability, binding affinity, nuclease resistance, bioavailability, and base-pair fidelity. These engineered nucleic acids are useful structural, functional, and mechanistic probes for disease detection, molecular sensing, and fundamental understanding of the structures and biological functions of nucleic acids (DNA and RNA). The structural, functional and spectroscopic repertoire of the nucleic acids can be further enhanced by strategic substitution of the oxygen atoms with selenium atoms. Selenium derivatization of nucleic acids generates modified biopolymers with unique structural and functional features that make them strong contenders for biochemical and biophysical research. The substitution of oxygen with selenium in the nucleobases permits a search for novel aspects of nucleic acid base-pairing and stacking interactions at the atomic level. Huang and co-workers have demonstrated that the single-atom modified (SAM) nucleosides and nucleic acids, where a single oxygen atom is strategically replaced with a selenium atom, are yellow colored and have over a 100 nm red-shift in the absorption maximum (1-3). With minimal structural perturbation, SAM nucleosides and nucleotides could be of immense significance in the detection and visualization of nucleic acids. Selenium-derivatized nucleic acids (SeNAs) could also serve as imperative tools in the structural, functional and mechanistic studies of nucleic acids and their complexes with proteins, small molecules, and/or metal ions. INDEX WORDS: Single-atom modification, Fluorescent nucleoside, Selenium derivatization, Biochemical and molecular probes, Visual detection, Nucleoside 5'-triphosphates, Thiol-modification MOLECULAR PROBE DESIGNS FOR NUCLEIC ACID BASED DETECTION