title: Lead discovery and optimization strategies for peptide macrocycles.
abstract: 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.
authors.affiliation: Ipsen Bioscience, Inc. 650 East Kendall Street, Cambridge, MA 02142, USA. Electronic address: abhijit.bhat@ipsen.com.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Bhat
authors.affiliation: Pfizer Worldwide Medicinal Chemistry, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. Electronic address: Lee.roberts@pfizer.com.
authors.forename: Lee R
authors.initials: LR
authors.lastname: Roberts
authors.affiliation: Ferring Research Institute, 4245 Sorrento Valley Blvd., San Diego, CA 92121, USA. Electronic address: John.dwyer@ferring.com.
authors.forename: John J
authors.initials: JJ
authors.lastname: Dwyer
mesh_terms: D003500:Cyclization; D055808:Drug Discovery; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D055550:Protein Stability
chemical_list: D047028:Macrocyclic Compounds; D010455:Peptides
keywords: Macrocycles; PPI; Peptides; Phage display; mRNA display