Selection-based discovery of macrocyclic peptides for the next generation therapeutics

• Macrocyclic peptides for the next generation therapeutics.
• Selection based-discovery from ribosomally expressed libraries.
• Ring-constrained structures with potent affinity or inhibitory activity.

Naturally occurring macrocyclic peptides represent a unique class of compounds that exhibit various biological activities ranging from antibiotics to immunosuppressant. Although the discovery of such macrocyclic peptides had relied on their isolation from living organisms, recent advances in ribosomal peptide synthesis and in display techniques made it possible to use artificially generated macrocyclic peptide libraries for selection of ligands for biologically relevant proteins. In this review, we discuss the technologies and their applications for the discovery of peptide ligands.