Thiophene-Extended Fluorescent Nucleosides as Molecular Rotor-Type Fluorogenic Sensors for Biomolecular Interactions

Fluorescent molecular rotors are versatile tools for the investigation of biomolecular interactions and the monitoring of microenvironmental changes in biological systems. They can transform invisible information into a fluorescence signal as a straightforward response. Their utility is synergistically amplified when they are merged with biomolecules. Despite the tremendous significance and superior programmability of nucleic acids, there are very few reports on the development of molecular rotor-type isomorphic nucleosides. Here, we report the synthesis and characterization of a highly emissive molecular rotor-containing thymine nucleoside (^ThexT) and its 2'-O-methyluridine analogue (2'-OMe-^ThexU) as fluorogenic microenvironment-sensitive sensors that emit vivid fluorescence via an interaction with the target proteins. ^ThexT and 2'-OMe-^ThexU may potentially serve as robust probes for a broad range of applications, such as fluorescence mapping, to monitor viscosity changes and specific protein-binding interactions in biological systems.