Investigating the druggability of the motif-mediated interactome with peptide PROTACs

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Short, Linear Motif (SLiMs) are ubiquitous compact interaction interfaces that direct key cellular processes. PROTACs targeting SLiM-binding pockets can specifically promote ubiquitin ligase-dependent degradation of regulatory proteins in critical cellular pathways. We will apply a scalable method using genetically encoded peptide PROTACs to provide proof of principle for the therapeutic relevance of targeted degradation of essential proteins. Peptide PROTACs provide a fast and cost-effective approach to mirror the mode of action of a small molecule PROTAC, providing evidence for the spatiotemporal compatibility of the E3 and target, and the phenotype of target protein degradation.