Berenil recognizes and changes the characteristics of adenine and thymine polynucleotide structures.
Using circular dichroism, differential scanning calorimetry and susceptibility to DNAse I cleavage assays, we show that the interaction of berenil, a minor-groove binding drug, with poly(dA-dT).poly(dA-dT) and poly(dA).poly(dT) involves important changes in the polynucleotide conformation. The effect of berenil on poly(dA-dT).poly(dA-dT) comprises a clear alteration in CD spectra even at drug/DNA ratios smaller than the stoichiometric value. Berenil recognizes and binds to the alternating-B conformation of DNA changing it to a new conformation which appears to show some of the peculiarities of poly(dA).poly(dT), possibly through a modification in the helical parameters at the TpA and ApT steps. Such alteration is accompanied by a small calorimetric enthalpy change. Moreover, the calorimetric enthalpy does not change significantly whatever the input ratio of drug to poly(dA-dT).poly(dA-dT), indicating that berenil binding does not substantially alters the enthalpy of transition. In addition to increasing the melting temperature of the polynucleotide, berenil reduces the cooperativity of the poly(dA-dT).poly(dA-dT) transition slightly more than either distamycin or netropsin.
Barceló
F
F
Departamento de Biología Fundamental, Universitat de Les Illes Balears, Palma de Mallorca, Spain.
Portugal
J
J
D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003850:Deoxyribonuclease I; D004133:Diminazene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011067:Poly dA-dT / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D011067:Poly dA-dT; D003850:Deoxyribonuclease I; C003915:diminazene aceturate; D004133:Diminazene