title: Small molecule transcription factor mimic.
abstract: Regulation of gene expression by transcription factors touches many aspects of eukaryotic biology, and its systematic, external control by organic molecules represents a challenge in chemistry. Here we report the design of a completely organic, nonpeptidic compound that mimics a transcription factor. The design takes advantage of the specific DNA-binding affinity of a hairpin polyamide molecule and the ability of wrenchnolol to bind to the Sur-2 subunit of human mediator complex. The hybrid compound of these two molecules activates transcription of a reporter gene in vitro in a promoter-dependent manner through simultaneous contacts with DNA and Sur-2. Our results indicate that it is possible to generate a transcription factor out of nonpeptidic components.
authors.affiliation: The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Arndt
authors.forename: Qian
authors.initials: Q
authors.lastname: Mao
authors.forename: Yongmun
authors.initials: Y
authors.lastname: Choi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D000218:Adamantane; D001360:Avidin / Q000737:chemistry / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007211:Indoles; D056892:Mediator Complex; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D020005:Propanols / Q000737:chemistry / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001952:Bridged-Ring Compounds; D004268:DNA-Binding Proteins; D007211:Indoles; C492159:MED23 protein, human; D056892:Mediator Complex; D009757:Nylons; D020005:Propanols; D015534:Trans-Activators; D014157:Transcription Factors; C486112:wrenchnolol; D001360:Avidin; D012319:RNA Polymerase II; D000218:Adamantane