Expanding the chemical biology toolbox: cyclic peptides emerging as versatile chemical probes

The present review provides a concise overview of cyclic peptides as chemical probes, including recent developments in their discovery and applications. Their 'goldilocks' physicochemical properties, selectivity, and affinity, as well as their range of discovery techniques and modular structure, position them as compelling tools within the chemical biology landscape. The selectivity and modularity of peptides in particular enable their adaptation into chemical tools and facilitate the exploration of their targets, as demonstrated by recent examples discussed herein. Given the growing interest in this area, the present review highlights selected examples from a rapidly expanding literature, reflecting the strength and versatility of this modality. As the field continues to mature, we can expect cyclic peptides to enable the exploration and validation of previously intractable targets and to support drug discovery efforts against novel targets. Notable challenges remain, particularly regarding cell permeability, although active research continues to advance the area. Cyclic peptides are well-placed to serve as a powerful complement to the existing chemical biology toolbox.