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Triple-helix formation and cooperative binding by oligodeoxynucleotides with a 3'-3' internucleotide junction

Triple-helix formation by oligodeoxynucleotides in a sequence-specific manner is limited to polypurine tracts of duplex DNA. To increase the number of biologically relevant targets for triple-helix formation, we have utilized oligodeoxynucleotides containing a 3'-3' internucleotide junctio...

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Bibliographic Details
Published in:Biochemistry (Easton) 1992-02, Vol.31 (6), p.1603-1609
Main Authors: Froehler, Brian C, Terhorst, Terry, Shaw, Jeng Pyng, McCurdy, Sarah N
Format: Article
Language:English
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Summary:Triple-helix formation by oligodeoxynucleotides in a sequence-specific manner is limited to polypurine tracts of duplex DNA. To increase the number of biologically relevant targets for triple-helix formation, we have utilized oligodeoxynucleotides containing a 3'-3' internucleotide junction to allow for binding to opposite strands of duplex DNA. Molecular modeling was used to aid in the design of the xylose dinucleoside linker 1 that is rigid and minimizes the number of conformers to minimize the entropy of binding. Thermal denaturation studies show that a 3'-3'-linked oligodeoxynucleotide, bearing nine nucleotides on each side of the linker, has a higher Tm (47.6 degrees C) than that of a 21-mer binding to a single polypurine tract (45.3 degrees C). Binding domain minimization studies and sequence-specific alkylation of a target duplex demonstrate a high degree of cooperativity between the two triple-helix binding domains, thus allowing for an increase in the number of biologically relevant targets for triple-helix formation.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00121a004