Development of a novel gel-display drug screening technique

• Project/Area Number: 15K16558
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: The University of Tokyo
• Principal Investigator: Passioura Toby 東京大学, 大学院理学系研究科(理学部), 特任助教 (60750239)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Chemical Biology / Peptide / Antibiotic / chemical biology / peptide / antibiotic

Outline of Final Research Achievements

The goal of this work was to identify new antibiotics for the treatment of drug resistant bacterial infections. We identified 16 candidate inhibitors of bacterial antibiotic-resistance enzymes. Four of which are highly potent and exhibited activity against enzymes from multiple different drug-resistant strains of bacteria. These compounds may be used to develop drugs for the treatment of antibiotic resistant bacterial infections.

Research Products

• [Journal Article] A RaPID way to discover nonstandard macrocyclic peptide modulators of drug targets. (2017)
  • Author(s): Passioura T and Suga H
  • Journal Title: Chem Commun (Camb) Volume: 53 Issue: 12 Pages: 1931-1940
  • DOI: 10.1039/c6cc06951g
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Drug-like macrocyclic peptides comprised of diverse non-canonical amino acids assembled through genetic code reprogramming. (2017)
  • Author(s): Passioura T
  • Organizer: 42nd Lorne Conference on Protein Structure and Function
  • Place of Presentation: Lorne, Australia
  • Year and Date: 2017-02-07
  • Int'l Joint Research
• [Presentation] Drug-like non-canonical cyclic peptides selected from diverse libraries. (2015)
  • Author(s): Toby Passioura
  • Organizer: 3rd International Conference on Circular Proteins
  • Place of Presentation: Moreton Island, QLD, Australia
  • Year and Date: 2015-11-03
• [Presentation] Ribosomal synthesis of highly N- and O-methylated cyclic peptide libraries for selection of protein-protein interaction inhibitors with “drug-like” characteristics. (2015)
  • Author(s): Toby Passioura
  • Organizer: 11th Australian Peptide Conference
  • Place of Presentation: Kingscliff, NSW, Australia
  • Year and Date: 2015-10-28