A potentially general method for the in vivo selection of inhibitory peptides targeted at a specific protein using yeast.

Although invaluable for biology and medicine, general methods for the selection of inhibitors directed against any protein activity are still missing. To test whether the fitness-based interferential genetics (FIG) approach performed in yeast might contribute to changing this situation, we used this method for the selection of artificial-gene-encoded peptides targeted at firefly luciferase, a foreign protein which was expressed in yeast. Some of these peptides were shown to inhibit the light-producing activity of luciferase in vitro. These results obtained within a totally artificial setting provide a direct demonstration of FIG selection for antagonistic components. Moreover, they open the way for FIG as a simple and general approach for selecting peptides against any specific protein activity expressed in a cellular environment, thus yielding compounds of potential scientific, medical and therapeutic value. Conditions for the development of such valuable compounds in the future using FIG are discussed.