Degron tags can trigger rapid and temporally controlled degradation of proteins using small molecules known as molecular glues. These molecular glues induce or stabilize protein interactions between a target protein and a ubiquitin ligase. As research tools, molecular glue complexes are limited by the large size of degron tags, which prevents integration in endogenous protein-coding genes. In a study published in Science, Mercer et al. apply a continuous evolution approach to generate molecular glue complexes with high affinities and smaller size, obtaining a compact degron that triggers protein degradation with no detectable off-target effects.

Recent work developed an optimized molecular glue, PT-179, that binds cereblon to trigger protein degradation. Unlike its predecessors, PT-179 does not degrade off-target proteins, making it an ideal starting block to design molecular glue complexes with improved properties.

降解决定子标签可以使用称为分子胶的小分子触发蛋白质的快速且暂时受控的降解。这些分子胶诱导或稳定靶蛋白和泛素连接酶之间的蛋白质相互作用。作为研究工具，分子胶复合物受到大尺寸降解决定子标签的限制，这阻止了内源蛋白质编码基因的整合。在《科学》杂志上发表的一项研究中，Mercer 等人。应用连续进化方法生成具有高亲和力和较小尺寸的分子胶复合物，获得紧凑的降解决定子，该降解决定子可触发蛋白质降解，且没有可检测到的脱靶效应。

最近的工作开发了一种优化的分子胶 PT-179，它可以结合 cereblon 以触发蛋白质降解。与其前身不同，PT-179 不会降解脱靶蛋白质，使其成为设计具有改进性能的分子胶复合物的理想起点。