Architectural Design of Phage‐Displayed Peptide Libraries for Peptide Discovery

Peptide phage display is a cornerstone technology in molecular engineering, providing a robust platform for the rapid discovery of high-affinity ligands. The rapid rise of peptides, especially in therapeutics, over recent years has shed light on the importance of phage display as a tool for peptide discovery. The evolution of peptide scaffolds from flexible linear sequences to structurally constrained architectures has expanded the scope of application of peptides in general. The review examines strategies used to generate monocyclic, bicyclic, and multicyclic peptides. These constrained formats mimic the complex loops of natural proteins, offering enhanced metabolic stability and superior binding affinity for challenging targets like protein-protein interaction interfaces. Furthermore, the review surveys the diverse applications ranging from targeted therapeutics and molecular diagnostics to the engineering of material-specific peptides for nanotechnology. Finally, we discuss current technical hurdles and the transformative potential of integrating next-generation sequencing and computational modeling to redefine the future of peptide discovery.