title: Identification of seco-clavilactone B as a small-molecule actin polymerization inhibitor.
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.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sasazawa
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Mogi
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takao
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Siro
authors.initials: S
authors.lastname: Simizu
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013912:Threonine / Q000378:metabolism
chemical_list: D000199:Actins; D007783:Lactones; D054852:Small Molecule Libraries; C522714:clavilactone B; D013912:Threonine; D003545:Cysteine
keywords: actin polymerization inhibitor; bioprobe; chemical biology; cytoskeleton; seco-clavilactone B