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

Abstract

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.