Identification of seco-clavilactone B as a small-molecule actin polymerization inhibitor

So Miyazaki; Yukiko Sasazawa; Takuma Mogi; Takehiro Suzuki; Keisuke Yoshida; Naoshi Dohmae; Ken Ichi Takao; Siro Simizu

doi:10.1002/1873-3468.12154

Identification of seco-clavilactone B as a small-molecule actin polymerization inhibitor

So Miyazaki, Yukiko Sasazawa, Takuma Mogi, Takehiro Suzuki, Keisuke Yoshida, Naoshi Dohmae, Ken Ichi Takao, Siro Simizu

Department of Applied Chemistry

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Phenotype-based chemical screening is an attractive strategy for the identification of bioactive compounds. We searched for a compound that induces cellular morphological change and identified a novel compound that we named seco-clavilactone B (Seco-CB). Treatment with Seco-CB decreased the ratio of filament actin (F-actin) to globular actin (G-actin). An in vitro actin polymerization assay revealed that Seco-CB inhibited actin polymerization directly. Further analysis demonstrated that the inhibitory effect of Seco-CB on actin polymerization was associated with Seco-CB binding to either Thr5 or Cys285 of actin. These data indicate that Seco-CB is a novel actin polymerization inhibitor.

Original language	English
Pages (from-to)	1163-1173
Number of pages	11
Journal	FEBS Letters
Volume	590
Issue number	8
DOIs	https://doi.org/10.1002/1873-3468.12154
Publication status	Published - 2016 Apr 1

Keywords

actin polymerization inhibitor
bioprobe
chemical biology
cytoskeleton
seco-clavilactone B

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1002/1873-3468.12154

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abstract = "Phenotype-based chemical screening is an attractive strategy for the identification of bioactive compounds. We searched for a compound that induces cellular morphological change and identified a novel compound that we named seco-clavilactone B (Seco-CB). Treatment with Seco-CB decreased the ratio of filament actin (F-actin) to globular actin (G-actin). An in vitro actin polymerization assay revealed that Seco-CB inhibited actin polymerization directly. Further analysis demonstrated that the inhibitory effect of Seco-CB on actin polymerization was associated with Seco-CB binding to either Thr5 or Cys285 of actin. These data indicate that Seco-CB is a novel actin polymerization inhibitor.",

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author = "So Miyazaki and Yukiko Sasazawa and Takuma Mogi and Takehiro Suzuki and Keisuke Yoshida and Naoshi Dohmae and Takao, {Ken Ichi} and Siro Simizu",

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AU - Miyazaki, So

AU - Sasazawa, Yukiko

AU - Mogi, Takuma

AU - Suzuki, Takehiro

AU - Yoshida, Keisuke

AU - Dohmae, Naoshi

AU - Takao, Ken Ichi

AU - Simizu, Siro

PY - 2016/4/1

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N2 - Phenotype-based chemical screening is an attractive strategy for the identification of bioactive compounds. We searched for a compound that induces cellular morphological change and identified a novel compound that we named seco-clavilactone B (Seco-CB). Treatment with Seco-CB decreased the ratio of filament actin (F-actin) to globular actin (G-actin). An in vitro actin polymerization assay revealed that Seco-CB inhibited actin polymerization directly. Further analysis demonstrated that the inhibitory effect of Seco-CB on actin polymerization was associated with Seco-CB binding to either Thr5 or Cys285 of actin. These data indicate that Seco-CB is a novel actin polymerization inhibitor.

AB - Phenotype-based chemical screening is an attractive strategy for the identification of bioactive compounds. We searched for a compound that induces cellular morphological change and identified a novel compound that we named seco-clavilactone B (Seco-CB). Treatment with Seco-CB decreased the ratio of filament actin (F-actin) to globular actin (G-actin). An in vitro actin polymerization assay revealed that Seco-CB inhibited actin polymerization directly. Further analysis demonstrated that the inhibitory effect of Seco-CB on actin polymerization was associated with Seco-CB binding to either Thr5 or Cys285 of actin. These data indicate that Seco-CB is a novel actin polymerization inhibitor.

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Identification of seco-clavilactone B as a small-molecule actin polymerization inhibitor

Abstract

Keywords

ASJC Scopus subject areas

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