University of Tokyo
Revolutionizing the Discovery Processes of de novo Bioactive Peptides and Biologics
Macrocyclic peptides possess a number of pharmacological characteristics distinct from other well-established therapeutic molecular classes, resulting in a versatile drug modality with a unique profile of advantages. Macrocyclic peptides are accessible by not only chemical synthesis but also ribosomal synthesis. Particularly, recent inventions of the genetic code reprogramming integrated with an in vitro display format, referred to as RaPID, Random non-standard Peptides Integrated Discovery, system, have enabled us to screen mass libraries, >1 trillion members, of non-standard peptides containing multiple non-proteinogenic amino acids, giving unique properties of peptides distinct from conventional peptides, for example greater proteolytic stability, higher affinity, low nM to sub nM dissociation constants, and superior pharmacokinetics.
The field is rapidly growing evidenced by increasing interests from industrial sectors, including small start-ups as well as mega-pharmas, toward drug development efforts on macrocyclic peptides, which has led to several de novo discovered peptides entering pre-clinical and clinical trials. This lecture discusses the aforementioned RaPID system and several showcases of therapeutic potentials of macrocyclic peptides generated by the Suga’s laboratory and collaborations with other laboratories.