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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2003-7-9
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pubmed:abstractText |
The sequence-specific inhibition of essential protein-DNA contacts in the promoter of a gene is a central issue for the regulation of gene expression by chemical methods. Hairpin polyamides have been shown to inhibit protein-DNA complexes in some but not all cases. For example, polyamides co-occupy the same DNA sequence in the minor groove in the presence of major-groove binding bZip proteins. Four hairpin polyamide-acridine conjugates were synthesized and shown to bind the minor groove of DNA with high affinity in a sequence-specific manner. The polyamide-acridine conjugates were shown to unwind DNA (phi = 14-15 degrees), evidence for intercalation by the acridine moiety. Importantly, the polyamide-intercalator conjugates, which combine sequence-specific groove binding with proximal local unwinding, inhibit major-groove DNA binding by the GCN4 bZip protein. This class of DNA binding molecules creates a sequence-specific allosteric change in DNA structure and has the potential to be a general inhibitor of transcription factor binding independent of the specific protein-DNA structure.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0002-7863
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
125
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8476-85
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12848553-Acridines,
pubmed-meshheading:12848553-Animals,
pubmed-meshheading:12848553-Base Sequence,
pubmed-meshheading:12848553-Basic-Leucine Zipper Transcription Factors,
pubmed-meshheading:12848553-Binding Sites,
pubmed-meshheading:12848553-Cattle,
pubmed-meshheading:12848553-DNA,
pubmed-meshheading:12848553-DNA-Binding Proteins,
pubmed-meshheading:12848553-G-Box Binding Factors,
pubmed-meshheading:12848553-Intercalating Agents,
pubmed-meshheading:12848553-Kinetics,
pubmed-meshheading:12848553-Molecular Sequence Data,
pubmed-meshheading:12848553-Nucleic Acid Conformation,
pubmed-meshheading:12848553-Nylons,
pubmed-meshheading:12848553-Substrate Specificity,
pubmed-meshheading:12848553-Thermodynamics,
pubmed-meshheading:12848553-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Allosteric inhibition of protein--DNA complexes by polyamide--intercalator conjugates.
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pubmed:affiliation |
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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