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

短，线性Motif （SLiMs）是无处不在的紧凑交互界面，指导关键的细胞过程。靶向SLiM-binding口袋的PROTACs可以特异性地促进关键细胞通路中泛素连接酶依赖性调节蛋白的降解。我们将采用一种可扩展的方法，使用基因编码肽PROTACs，为必需蛋白靶向降解的治疗相关性提供原理证明。肽PROTAC提供了一种快速、经济的方法来反映小分子PROTAC的作用模式，为E3和靶点的时空相容性以及靶蛋白降解的表型提供了证据。

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.