Structural requirement of tunicamycin V for MraY inhibition

Kazuki Yamamoto; Akira Katsuyama; Satoshi Ichikawa

doi:10.1016/j.bmc.2019.02.035

Structural requirement of tunicamycin V for MraY inhibition

Bioorg Med Chem. 2019 Apr 15;27(8):1714-1719. doi: 10.1016/j.bmc.2019.02.035. Epub 2019 Mar 2.

Authors

Kazuki Yamamoto¹, Akira Katsuyama², Satoshi Ichikawa³

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
² Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
³ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: ichikawa@pharm.hokudai.ac.jp.

PMID: 30850266
DOI: 10.1016/j.bmc.2019.02.035

Abstract

Elucidating a structure-activity relationship study by evaluating a series of truncated analogues is a simple but important and effective tactic in medicinal chemistry based on natural products with a large and complex chemical structure. In this study, a series of truncated analogues of tunicamycin V were designed and synthesized and their MraY inhibitory activity was investigated in order to gain insight into the effect of these moieties on MraY inhibition.

Keywords: Antibacterial; Enzyme inhibitor; Natural products; Nucleoside; Structure-activity relationship.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / metabolism
Bacterial Proteins / antagonists & inhibitors*
Bacterial Proteins / metabolism
Biological Products / chemistry
Biological Products / metabolism
Drug Design
Inhibitory Concentration 50
Staphylococcus aureus / enzymology
Transferases (Other Substituted Phosphate Groups)
Transferases / antagonists & inhibitors*
Transferases / metabolism
Tunicamycin / chemistry*
Tunicamycin / metabolism

Substances

Anti-Bacterial Agents
Bacterial Proteins
Biological Products
Tunicamycin
Transferases
Transferases (Other Substituted Phosphate Groups)
mraY protein, Bacteria