C01 • Boron-Nitrogen Heterocycles as Fluorescent Labels for Nucleic Acids

Chemically modified nucleosides are of increasing interest, for example as fluorescent probes of nucleic acid structure and function. Polycyclic aromatic hydrocarbons (PAHs) including pyrene and perylene have previously been used as fluorescent reporters in nucleosides and nucleic acids, but have encountered limitations due to the hydrophobic nature and short wavelength emission. The prospect for tuning the electronic and photophysical properties of PAHs by replacing selected CC units with their isoelectronic BN pairs inspired us to explore BN-PAHs as a new class of nucleobase modifications.
We propose to synthesize novel BN-PAH-derived nucleosides and oligonucleotides and explore their structural and photophysical properties. The local effects of the BN isostere on the nature of the nucleobase surrogate are expected to influence excimer formation, and result in distinct readouts of structural changes in the DNA (e.g. upon hybridization, triplex or quadruplex formation, or assembly into larger nucleic acid architectures). The resulting oligonucleotides are further considered as components for strand displacement assays and hybridization chain reactions in synthetic biology and DNA nanotechnology. In the direction of chemical biology, a long-term perspective for BN-PAH-nucleic acids is their use in fluorescent assays to study DNA repair or the activity RNA-modifying enzymes.