Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these ‘bifunctional’ small molecules facilitate the study of an increasingly wide range of complex biological phenomena and enable the drugging of otherwise challenging therapeutic targets and processes. Despite their structural and functional differences, all bifunctional molecules employ Nature’s strategy of altering interactomes and inducing proximity to modulate biology. They therefore exhibit a shared set of chemical and biophysical principles that have not yet been appreciated fully. By highlighting these commonalities—and their wide-ranging consequences—we hope to chip away at the artificial barriers that threaten to constrain this interdisciplinary field. Doing so promises to yield remarkable benefits for biological research and therapeutics discovery.

大自然使用各种工具来介导细胞中的信息流，其中许多工具控制关键生物大分子之间的距离。研究人员因此产生了其活性源于同时与两种（或更多）蛋白质相互作用的化合物。在本视角中，我们描述了这些“双功能”小分子如何促进对日益广泛的复杂生物现象的研究，并能够对其他具有挑战性的治疗靶点和过程进行药物治疗。尽管结构和功能存在差异，但所有双功能分子都采用了改变相互作用组和诱导接近来调节生物学的自然策略。因此，它们表现出一套共同的化学和生物物理原理，但尚未得到充分认识。通过强调这些共性及其广泛的影响，我们希望消除可能限制这一跨学科领域的人为障碍。这样做有望为生物研究和治疗发现带来显着的效益。