Binding of netropsin to a DNA triple helix.
The interaction of netropsin, a minor groove binding drug, with T-A-T triple helix and A-T double helix was studied using circular dichroism spectroscopy and thermal denaturation. The triple helix was made by an oligonucleotide (dA)12-x-(dT)12-x-(dT)12, where x is a hexaethylene glycol chain bridged between the 3' phosphate of one strand and the 5' phosphate of the following strand. This oligonucleotide is able to fold back on itself to form a very stable triplex. Changing the conditions allows the same oligonucleotide in a duplex form with a (dT)12 dangling arm. Circular dichroism spectroscopy demonstrates that netropsin can bind to the triple helical structure. Spectral analysis shows that the bound drug exhibits a conformation and an environment similar in double-stranded and in triple-stranded structure. However, the binding constant to the triple-stranded structure is found smaller than the binding constant to the double-stranded one. Thermal denaturation experiments demonstrate that netropsin destabilizes the triplex whereas it stabilizes the duplex.
Durand
M
M
Centre de Biophysique Moléculaire 1A, Orléans, France.
Thuong
N T
NT
Maurizot
J C
JC
D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D046911:Macromolecular Substances; D008433:Mathematics; D008961:Models, Structural; D008969:Molecular Sequence Data; D009429:Netropsin / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013816:Thermodynamics
D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D009429:Netropsin; D004247:DNA