Simultaneous binding of a polyamide dimer and an oligonucleotide in the minor and major grooves of DNA.
The effect of the polyamide ImPyPy-Dp (Im = N-methylimidazole-2-carboxamide, Py = N-methylpyrrole-2-carboxamide, and Dp = dimethylaminopropylamide), which binds as an antiparallel dimer in the Watson-Crick minor groove, on pyrimidine. purine.pyrimidine triple helix stability was investigated. A DNA restriction fragment was designed which contained two triple helix sites, one which overlapped a minor groove ligand site (proximal), and a control site 13 base pairs away (distal). Using quantitative DNase I footprint titration experiments the equilibrium association constant of oligonucleotide 5'-TTTTTm5CTTTm5CTTTm5CT-3' (1) to each site was measured in the absence and presence of the polyamide dimer. Our data indicate that triple helix formation is compatible with a polyamide dimer binding in the minor groove of DNA at an overlapping site. No cooperative effect of the polyamide dimer on the equilibrium association constant of oligonucleotide 1 was observed.
Parks
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Divison of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Dervan
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D001345:Autoradiography; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D004214:Distamycins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009429:Netropsin / Q000031:analogs & derivatives* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism*
D004214:Distamycins; D009757:Nylons; D009841:Oligonucleotides; C076037:1-methylimidazole-2-carboxamide netropsin; D009429:Netropsin; C030000:stallimycin; D004247:DNA