Interaction of a spin-labeled adenine-acridine conjugate with a DNA duplexcontaining an abasic site model

The abasic sire is a common lesion in DNA that is also formed as an interme diate in the base excision repair of damaged bases. We have previously repo rted the adenine-acridine conjugate 1 that was designed to bind to the abas ic site and interfere with the repair process. High-field NMR had shown tha t 1 forms specific complexes with a DNA duplex containing an apurinic abasi c site model. We report here the dynamics of the interaction of the nitroxi de-labeled analogue 3 of the conjugate 1 with the same apurinic oligonucleo tide and with the parent unmodified, duplex. Identical study of the labeled acridine subunit 5 used as a reference is also reported. In the presence o f the apurinic duplex and depending on the concentrations and drug ratios, three species are observed: the radical "free in solution", the "intercalat ion" complex characterized by its similarity to that observed in the presen ce of the parent unmodified duplex, and the "abasic-site-specific" complex which is the sole species visible at low drug ratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculatio n of correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii) complexation of the drug is little or not mo dified by the spin-label. We also show that the abasic site constitutes a b inding site for the. propylaminoacridine intercalator 5.