Targeted protein degradation aims to hijack endogenous protein quality control systems to achieve direct knockdown of protein targets. This exciting technology utilizes event-based pharmacology to produce therapeutic outcomes, a feature that distinguishes it from classical occupancy-based inhibitor agents. Early degrader candidates display resilience to mutations while possessing potent nanomolar activity and high target specificity. Paired with the rapid advancement of our knowledge in the factors driving targeted degradation, the expansion of this style of therapeutic agent to a range of disease indications is eagerly awaited. In particular, the area of antibiotic discovery is sorely lacking in novel approaches, with the Antimicrobial Resistance (AMR) crisis looming as the next potential global health calamity. Here, the current advances in targeted protein degradation are highlighted, and potential approaches for designing novel antimicrobial protein degraders are proposed, ranging from adaptations of current strategies to completely novel approaches to targeted protein degradation.

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靶向蛋白质降解：抗菌药物发现的新前沿？

靶向蛋白质降解旨在劫持内源性蛋白质质量控​​制系统，以实现对蛋白质靶标的直接敲低。这项激动人心的技术利用基于事件的药理学来产生治疗效果，这一特征使其有别于经典的基于占用的抑制剂药物。早期降解剂候选物显示出对突变的弹性，同时具有有效的纳摩尔活性和高目标特异性。随着我们在驱动靶向降解的因素方面知识的快速进步，人们迫切期待将这种治疗药物扩展到一系列疾病适应症。特别是，抗生素发现领域严重缺乏新方法，抗菌素耐药性 (AMR) 危机即将成为下一个潜在的全球健康灾难。这里，