Synthesis of Fluorescent Nucleic Acids bearing Nucleobases Modified with Heteroaryl Group and Fluorophores

In recent years, fluorescent nucleobase analogs have received a great deal of attention due to their unique photophysical properties as well as their potential usefulness as probes for the higher order structures of nucleic acids. One of the approach to develop fluorescent nucleobase is to directly attach a heteroaromatic group to a nucleobase. Because the heteroaromatic group introduced to the nucleobase can freely rotate, the photophysical properties of the fluorescent nucleobase, thus developed, can change depending on the environment or the interaction with other molecules which affect the rotation of the heteroaromatic group. Such environment sensitive fluorescent bases are called 'molecular rotors', and expected as the useful fluorescent probes for monitoring the nucleic acids-nucleic acids interactions or nucleic acids-protein interactions. This article describes the synthesis and photophysical properties of the 'molecular rotor' fluorescent nucleobases developed by us. Especially, the uracil derivatives bearing a benzofuran or a 3-methyl-benzofuran ring at the position 5, and 7-deazaguanine derivative bearing a benzofuran ring at the position 7 are described. In addition, a unique fluorescent uracil derivative bearing 3-(4-hydroxy-benzilidene) imidazolinone skeletones, which are mimic of chromophore of green fluorescent protein, at the position 5 is also described.