Solvatochromic peptidic binder obtained via extended phage display acts as a fluororeporter for fragment-based drug discovery (FBDD)

We have previously established a selection system to obtain a solvatochromic protein binder from a peptidic fluoroprobe library via the extended T7 phage display. Here, we use the peptidic binder as a fluororeporter in this proof-of-concept study of fragment-based screening approach to drug discovery. The binder is released from the target protein on mixing with an appropriate lead compound, thereby altering its fluorescence color/intensity under 365 nm ultraviolet wavelength irradiation . By this instant screening outcome, the affinity of the lead compound is apparent to the naked eye, and quantified with a portable microvolume fluorophotometer. We envision that our simple and affordable screening system will provide opportunities for early stage drug discovery, especially for non-experts in academia and education because expensive hardware is not required for qualifying the measurements. Graphical abstract