Targeting of extracellular protein–protein interactions with macrocyclic peptides

Targeting of extracellular protein–protein interactions (PPI) is emerging as a major application for de novo discovered macrocyclic peptides. Modern discovery platforms can routinely identify peptide ligands capable highly selective modulation signaling pathways; amenability to chemical synthesis and natural modularity peptides additionally provides an avenue their further structural elaboration, while the challenge cell internalization be minimized. Here, we discuss recent progress in targeting PPIs with by focusing on number case studies. We analyze scope potential limitations systems identifying functional ligands. also highlight technical advancements allowing more streamlined pipeline our brief perspective this field.