Hydrogen bonding in deoxyribonucleic acid base recognition. 1. Proton nuclear magnetic resonance studies of...

For studies on the possible involvement of hydrogen bonding in base recognition from the outside of the nucleic acid double helix, 2-methoxy-6-chloro-9-aminoacridine derivatives bearing a carboxamide side chain were examined by 1H NMR spectroscopy. The study of the interaction of these derivatives with CpG or GpC demonstrated that (i) the 2-methoxy-6-chloro-9-aminoacridine ring intercalates preferentially in the minihelix formed by CpG, which indicates a relative pyrimidine-(3'-5')-purine sequence specificity that contrasts with the simple 9-aminoacridine ring wherein Reuben et al. [Reuben, J., Baker, B. M., & Kallenbach, N. R. (1978) Biochemistry 17, 2916-2919] did not observe any sequence preference (ii) the geometry of the intercalated minihelical complex of the 2-methoxy-6-chloro-9-[(5-carbamolypentyl)-amino]acridine with CpG as deduced from isoshielding curves resembles that found in the crystalline complexes of proflavin, with several autocomplementary dinucleoside monophosphates, (iii) the terminal carboxamide group borne by the side chain of 2-methoxy-6-chloro-9-[(5-carbamoylpentyl)amino]acridine (5) intercalated in CpG lies in the small groove and seems to interact through hydrogen bonds with the adjacent guanine.