Lead discovery and optimization strategies for peptide macrocycles.

Peptide macrocycles represent a chemical space where the best of biological tools can synergize with the best of chemical approaches in the quest for leads against undruggable targets. Peptide macrocycles offer some key advantages in both lead discovery and lead optimization phases of drug discovery when compared to natural product and synthetic macrocycles. In addition, they are uniquely positioned to capitalize on the therapeutic potential of peptides because cyclization can help drive selectivity, potency and overcome the common limitations of metabolic instability of peptides.