title: 12 Arylstibonic acids that inhibit the DNA binding of five B-ZIP dimers.
abstract: Previously, we identified an arylstibonic acid, NSC13778 that specifically binds to the basic region of the C/EBPalpha B-ZIP domain and disrupts DNA binding. We now examine a panel of 14 additional arylstibonic acid derivatives of NSC13778 for their ability to inhibit the DNA binding of five B-ZIP dimers (c-Fos|JunD, VBP, C/EBPalpha, C/EBPbeta, and CREB). They show various specificities at inhibiting the DNA binding of five B-ZIP domains. NSC13746 inhibits the DNA binding of C/EBPbeta and CREB at 100nM and promiscuously inhibiting the DNA binding of all five proteins in the 1muM range. Dialysis experiments indicate that NSC 13746 binding to the B-ZIP domain is reversible. Thermal denaturation studies indicate that NSC13746 binds the B-ZIP domain. Some compounds specifically inhibit DNA binding, with VBP and c-Fos|JunD being most easily disrupted. These compounds inhibit, with similar specificities to the pure B-ZIP domains, the DNA binding of nuclear extract to the AP1 DNA sequence but no inhibition is observed to SP1 containing oligonucleotide. Transient transfection assays indicate that NSC13746 can inhibit the TPA induced activation of two B-ZIP dependent reporters. These experiments suggest that arylstibonic acids are promising leads for inhibiting the DNA binding of a group of B-ZIP proteins in cells.
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Building 37, Room 3128, Bethesda, MD 20892, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Rishi
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Oh
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Heyerdahl
authors.forename: Jianfei
authors.initials: J
authors.lastname: Zhao
authors.forename: Dominic
authors.initials: D
authors.lastname: Scudiero
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
mesh_terms: D000143:Acids / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000965:Antimony / Q000737:chemistry* / Q000378:metabolism*; D002934:Cinnamates / Q000737:chemistry* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D011489:Protein Denaturation; D055503:Protein Multimerization
chemical_list: D000143:Acids; D002934:Cinnamates; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C550834:NSC 13778; D004247:DNA; D000965:Antimony