NMR and molecular modeling studies of the interaction of artificial AP lyases with a DNA duplex containing an apurinic abasic site model.

Tailor-made molecules, DTAc and ATAc, that incorporate a nucleic base (adenine or 2,6-diaminopurine) linked by a diamino chain to an intercalator (9-amino-6-chloro-2-methoxyacridine) selectively recognize and efficiently cleave abasic sites in DNA via a β-elimination reaction. The three-dimensional structure of the complexes of DTAc and ATAc bound to a DNA undecamer, the 5‘d(C1G2C3A4C5X6C7A8C9G10C11)3‘·3‘d(G22C21G20T19 G18T17G16T15G14C13G12)5‘ duplex in which the X residue is a stable abasic site [3-hydroxy-2-(hydroxymethyl)tetrahydrofuran], has been studied by combined NMR−energy minimization methods. Analysis of the NMR spectra reveals that DTAc and ATAc interact with a very similar fashion and form two different complexes with DNA, present in a ratio of 70/30 (±10). In both complexes, the acridine ring intercalates exclusively between the C3·G20 and A4·T19 base pairs, the linker is located in the minor groove, and the base moiety docks in the abasic site. The principal difference between the major and ...