LMB Seminar - De-novo discovery of macrocyclic peptides and pseudo-natural products for therapeutic innovation

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• Hiroaki Suga - The University of Tokyo
• Monday 29 September 2025, 11:00-12:00
• In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoom link https://mrc-lmb-cam-ac-uk.zoom.us/j/96488916942?pwd=BpCGRwD8hD8ec89yfaJ0yKPmV3o6lv.1.

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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 mRNA-encoding display format, referred to as RaPID (Random non-standard Peptides Integrated Discovery) system, have enabled us to screen mass libraries consisting of over 1 trillion members of non-standard peptides containing multiple non-proteinogenic amino acids, giving unique properties of macrocyclic pseudo-natural 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 as a new modality group. This lecture discusses their screening by the RaPID system, and several showcases of therapeutic potentials of such molecules. This lecture also discusses the most recent advance in the display of de novo pseudo-natural products generated by thiopeptide’s post-translationally modifying enzymes.

This talk is part of the MRC LMB Seminar Series series.

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• In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoom link https://mrc-lmb-cam-ac-uk.zoom.us/j/96488916942?pwd=BpCGRwD8hD8ec89yfaJ0yKPmV3o6lv.1
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