Inducing biomolecular interactions with synthetic molecules to impact biological function is a concept of enormous appeal. Recent years have seen a resurgence of interest in designing bispecific molecules that serve as bridging agents to bring proteins together. Pioneering structural and biophysical investigation of ternary complexes formed by mono-functional and bifunctional ligands highlights that proximity-induced stabilization or de novo formation of protein-protein interactions is a common feature of their molecular recognition. In this review, we illustrate these concepts and advances with representative case studies, and highlight progress over the past three years, with particular focus on recruitment to E3 ubiquitin ligases by 'molecular glues' and chimeric dimerizers (PROTACs) for targeted protein degradation. This approach promises to significantly expand the range of tractable targets for chemical biology and therapeutic intervention.

中文翻译：

---

双功能化学探针诱导蛋白质-蛋白质相互作用。

诱导与合成分子的生物分子相互作用以影响生物学功能是一个极具吸引力的概念。近年来，人们对重新设计双特异性分子作为桥联剂以将蛋白质结合在一起的兴趣再次兴起。对由单官能和双官能配体形成的三元复合物进行的结构和生物物理研究表明，邻近诱导的蛋白质-蛋白质相互作用的稳定化或从头形成是其分子识别的共同特征。在这篇综述中，我们将通过代表性的案例研究来说明这些概念和进展，并重点介绍过去三年中的进展，特别着重于通过“分子胶”和嵌合二聚体（PROTAC）招募E3泛素连接酶来靶向蛋白质降解。