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| - Interaction of a Spin-Labeled Adenine−Acridine Conjugate with a DNA DuplexContaining an Abasic Site Model
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| - The abasic site is a common lesion in DNA that is also formed as an intermediate in the baseexcision repair of damaged bases. We have previously reported the adenine−acridine conjugate 1 thatwas designed to bind to the abasic site and interfere with the repair process. High-field NMR had shownthat 1 forms specific complexes with a DNA duplex containing an apurinic abasic site model. We reporthere the dynamics of the interaction of the nitroxide-labeled analogue 3 of the conjugate 1 with the sameapurinic oligonucleotide and with the parent unmodified duplex. Identical study of the labeled acridinesubunit 5 used as a reference is also reported. In the presence of the apurinic duplex and depending onthe concentrations and drug ratios, three species are observed: the radical “free in solution”, the“intercalation” complex characterized by its similarity to that observed in the presence of the parentunmodified duplex, and the “abasic-site-specific” complex which is the sole species visible at low drugratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculationof correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii)complexation of the drug is little or not modified by the spin-label. We also show that the abasic siteconstitutes a binding site for the propylaminoacridine intercalator 5.
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