A model for the ability of drugs to induce enhanced DNase I cleavage.
A common property of sequence-selective DNA-binding drugs lies in their ability to induce an enhanced DNase I cleavage in regions surrounding their binding sites. A hypothetical model to explain the enhancements induced by drug binding to the minor-groove of DNA is presented. It involves the participation of three different single models: a mass action effect produced by the enzyme redistribution after drug binding; changes in the minor groove width size; and interactions between the enzyme and the drug, so increasing the cleavage in places located close to the binding site. The model is tested by using statistical data analysis. The hypothetical model might explain the experimental results better than any of the single models alone, but these models also appear to render significant results.
Portugal
J
J
Departamento de Bioquímica y Fisiología, Universidad de Barcelona, Facultad de Quimica, Spain.
D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D009429:Netropsin / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012044:Regression Analysis
D006146:Guanidines; D004364:Pharmaceutical Preparations; D009429:Netropsin; D004247:DNA; D003850:Deoxyribonuclease I