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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adamantane
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Avidin / chemistry
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Avidin / metabolism
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Biomimetic Materials / chemical synthesis
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Biomimetic Materials / chemistry*
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Biomimetic Materials / metabolism
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism
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Humans
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Indoles
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Mediator Complex
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Nylons / chemical synthesis
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Nylons / chemistry*
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Nylons / metabolism
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Propanols / chemistry
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Propanols / metabolism
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RNA Polymerase II / metabolism
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Trans-Activators
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Transcription Factors / chemical synthesis
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Transcription Factors / chemistry*
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Transcription Factors / metabolism
Substances
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Bridged-Ring Compounds
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DNA-Binding Proteins
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Indoles
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MED23 protein, human
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Mediator Complex
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Nylons
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Propanols
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Trans-Activators
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Transcription Factors
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wrenchnolol
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Avidin
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RNA Polymerase II
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Adamantane