Groundbreaking studies in protein biophysics have identified the mechanisms of transmembrane signaling at the level of druggable protein–protein interactions (PPIs). This resulted in the development of the signaling chain homooligomerization (SCHOOL) strategy to modulate cell responses using receptor-specific peptides. Inspired by nature, these short peptides use ligand-independent mechanisms of receptor inhibition and demonstrate potent efficacy in vitro and in vivo. The SCHOOL strategy is especially important when receptor ligands are unknown. An example is the triggering receptor expressed on myeloid cells-1 (TREM-1) receptor, an emerging therapeutic target involved in the pathogenesis of most inflammatory diseases. Here, I discuss advances in the field with a focus on TREM-1 inhibitory SCHOOL peptides that offer new hope for a ‘magic bullet’ cure for cancer, arthritis, sepsis, retinopathy, and other medical challenges.

蛋白质生物物理学的突破性研究已经确定了可药物蛋白质-蛋白质相互作用 (PPI) 水平的跨膜信号传导机制。这导致了信号链同源寡聚化 (SCHOOL) 策略的发展，以使用受体特异性肽调节细胞反应。受大自然的启发，这些短肽使用不依赖于配体的受体抑制机制，并在体外和体内表现出强大的功效。当受体配体未知时，学校策略尤其重要。一个例子是髓样细胞 1 (TREM-1) 受体上表达的触发受体，这是一种涉及大多数炎症性疾病发病机制的新兴治疗靶点。在这里，我重点讨论该领域的进展，重点是 TREM-1 抑制性 SCHOOL 肽，它为治疗癌症、关节炎、败血症、视网膜病和其他医学挑战的“灵丹妙药”带来了新希望。