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

短线性基序（SLiM）是无处不在的紧凑的相互作用界面，直接的关键细胞过程。靶向SLiM结合口袋的PROTAC可以特异性地促进关键细胞途径中调节蛋白的泛素连接酶依赖性降解。我们将应用一种可扩展的方法，使用基因编码的肽PROTAC，为必需蛋白质的靶向降解的治疗相关性提供原理证明。肽PROTAC提供了一种快速且具有成本效益的方法来反映小分子PROTAC的作用模式，为E3和靶标的时空相容性以及靶蛋白降解的表型提供证据。

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.