title: Controlling gene expression by zinc(II)-macrocyclic tetraamine complexes.
abstract: The zinc(II) complexes of 12-membered macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two aryl-methyl group(s) (quinolyl-methyl, naphthyl-methyl, and acridinyl-methyl) selectively bind to thymines in a TATA box of the SV40 early promoter region and thus inhibit the binding of a transcriptional factor, TATA binding protein. These Zn2+-cyclen derivatives also act as inhibitors of DNA-targeted enzymes, type I and type II topoisomerases. They also exhibited strong antimicrobial activities for the gram-positive bacterial strain. These biochemical and biological properties were compared with those of conventionally established AT-recognizing drugs, distamycin A and DAPI. The Zn2+-cyclen complexes are a new type of small molecular, genetic transcriptional regulation factor.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Medicine, Hiroshima University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kikuta
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.forename: E
authors.initials: E
authors.lastname: Kimura
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004214:Distamycins / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D016385:TATA Box / Q000187:drug effects; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D004214:Distamycins; D006573:Heterocyclic Compounds, 1-Ring; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C030000:stallimycin; D004247:DNA; D004264:DNA Topoisomerases, Type I; D015032:Zinc