Pseudo-natural peptides, products and neobiologics for therapeutic applications

Macrocyclic peptides possess attractive 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, e.g. greater proteolytic stability, higher affinity (low nM to sub nM dissociation constants similar to antibodies), and superior pharmacokinetics.

The field is rapidly growing evidenced by increasing interests from industrial sectors, including mega-pharmas, toward drug development efforts on macrocyclic peptides and more recently extended to pseudo-natural products.

This lecture discusses the aforementioned screening technology, the RaPID system, and several showcases of therapeutic potentials of macrocyclic peptides. This lecture also discusses the most recent advance in the development of neobiologics using LassoGraft technology.

Professor Hiroaki Suga holds a Ph.D. from the Massachusetts Institute of Technology, and currently serves as a professor in the Department of Chemistry at the University of Tokyo. In 2022, he was appointed President of the Chemical Society of Japan and is an active member of the Council of Science, Technology, and Innovation under the Cabinet Office of Japan.
Professor Suga's achievements as a researcher, teacher, and leader in science and technology have been recognized with several honors and awards. In 2012, he received the President Award from the Science Council of Japan for his innovative contributions to government-industry-academic relations. He was honored with the Japan Innovator Award in 2016, and in 2023, he was awarded the prestigious Wolf Prize in Chemistry.