Design, synthesis and conformation-activity relationship analysis of LNA/BNA-type 5′-O-aminoribosyluridine as MraY inhibitors

Shintaro Kusaka, Kazuki Yamamoto, Motoko Shinohara, Yusuke Minato, Satoshi Ichikawa

Research output: Contribution to journalArticlepeer-review

Abstract

It is important to understand and control the biologically active conformation in medicinal chemistry. Muraymycins and caprazamycins, which are strong inhibitors of MraY, are promising antibacterial agents with a novel mode of action. Focusing on a sugar puckering and a dihedral angle ϕ of the uridine moiety of these natural products, LNA/BNA-type 5′-O-aminoribosyluridine analogues, whose puckering of the ribose moiety are completely restricted to the N-type, were designed and synthesized as simplified MraY inhibitors. Their conformation-activity relationship was further investigated in details. The conformation-activity relationship analysis investigated in this study could be a general guideline for simplification and rational drug design of MraY inhibitory nucleoside natural products.

Original languageEnglish
Article number116744
JournalBioorganic and Medicinal Chemistry
Volume65
DOIs
Publication statusPublished - 01-07-2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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