Visualization of Drug-Nucleic Acid Interactions at Atomic Resolution V. Structure of Two Aminoacridine/Dinucleoside Monophosphate Crystalline Complexes, Proflavine: 5-Iodocytidylyl(3'-5') Guanosine and Acridine Orange: 5-Iodocytidylyl(3'-5') Guanosine

摘要

Acridine orange and proflavine form complexes with the dinucleoside monophosphate, 5-iodocytidylyl(3'-5') guanosine (iodoCpG). The acridine orange-iodoCpG crystals are monoclinic, space group P2 sub 1 , with unit cell dimensions a = 14.36 A, b = 19.64 A, c = 20.67 A, beta = 102.5. The proflavine-iodoCpG crystals are monoclinic, space group C2, with unit cell dimensions a = 32.14 A, b = 22.23 A, c = 18.42 A, beta = 123.3. Both structures have been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares. Acridine orange forms an intercalative structure with iodoCpG but the acridine nucleus lies asymmetrically in the intercalation site. This asymmetric intercalation is accompanied by a sliding of base-pairs upon the acridine nucleus. Base-pairs above and below the drug are separated by about 6.8 A and are twisted about 10 exp 0 . Proflavine demonstrates symmetric intercalation with iodoCpG. Hydrogen bonds connect amino- groups on proflavine with phosphate oxygen atoms on the dinucleotide. Base-pairs above and below the intercalative proflavine molecule are twisted about 36 exp 0 . The altered magnitude of this angular twist reflects the sugar puckering pattern that is observed. We propose a proflavine-DNA and an acridine orange-DNA binding model. We will describe these models in detail in this paper. (ERA citation 04:039245)