title: [Design, synthesis, and structure-activity relationship study of organoantimony compounds that induce the expression of perlecan in vascular endothelial cells].
abstract: Organometallic compounds and complexes possibly show novel bioactivities unprecedented with organic molecules that consist of C, H, O, and N atoms. We have already reported that an organoantimony compound selectively induces the expression of perlecan, a large heparin sulfate proteoglycan, in cultured vascular endothelial cells. Perlecan consists of a core protein with Mr of approximately 400 kDa and three anticoagulant heparan sulfate glycosaminoglycan chains. However, little is known about the molecular mechanisms of perlecan expression in endothelial cells. Since an organoantimony compound induces the expression of perlecan, we prepared a variety of its derivatives and tried to identify the binding proteins for the organoantimony compound by the drug affinity responsive target stability method, a negative selection method to identify the target proteins. As the results, we found glucocoriticoid receptor as binding protein of the organoantimony compound, which mediates the expression of perlecan in endothelial cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Naka
authors.forename: Ryo
authors.initials: R
authors.lastname: Takita
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
mesh_terms: D000818:Animals; D000965:Antimony / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis*; D006801:Humans; D055601:Organic Chemistry Phenomena; D013329:Structure-Activity Relationship
chemical_list: D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D000965:Antimony