Masayuki Inoue

Masayuki Inoue

The University of Tokyo
 (83) 3-5841-1354


Talk Title: Development of a Strategy for Discovery of Superior Analogues of Antimicrobial Natural Products

Here we report a novel strategy for the discovery of potent antibiotics by preparing thousands of analogues of a highly complex natural product. Lysocin E, 1, a 37-membered natural peptide, induces rapid bacteriolysis of methicillin-resistant Staphylococcus aureus, MRSA. We designed the one-bead-one-compound approach, in which each bead carried a structurally unique analogue in submicrogram quantity, to produce a 1-based library consisting of 2401 bead-linked cyclic peptides.


By developing a new high throughput method that integrates submicrogram-scale solid-phase total synthesis, split-and-mix randomization, tandem mass spectrometry-sequencing, and miniaturized assays, we determined 26 candidates. Re-synthesis of these candidates in milligram scale disclosed that 11 artificial analogues exhibited antimicrobial activity more potent than or comparable to that of 1. Because of their high potency, newly discovered peptides will serve as highly promising seeds for the development of pharmaceuticals to treat various infectious diseases.


Masayuki Inoue


Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan


Lysocin E is a New Antibiotic that Targets Menaquinone in the Bacterial Membrane
K. Sekimizu et al. Nat. Chem. Biol. 2015, 11, 127-133

Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and its Enantiomeric, Epimeric, and N-Demethylated Analogues.
Inoue et al. Angew. Chem., Int. Ed. 2015, 54, 1556-1560

Total Synthesis and Functional Evaluation of Fourteen Derivatives of Lysocin E: Importance of Cationic, Hydrophobic, and Aromatic Moieties for Antibacterial ActivityM.
Inoue et al. Chem. Eur. J. 2016, 22, 16912–16919

Lecture Images

Masayuki Inoue presenting at APS2019 Masayuki Inoue presenting at APS2019 Masayuki Inoue presenting at APS2019