Variable role of ions in two drug intercalation complexes of DNA

Abstract

The crystal structures of the hexamer duplex d(CGTACG)(2) complexed with the intercalating anthraquinone derivative 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione and the acridine derivative 9-acridinyl tetralysine have been solved at 2.0- and 1.4-A resolution, respectively. In both cases, the drugs adopt multiple orientations within a large DNA cavity constituted by two groups of four approximately coplanar bases. Cations play a pivotal role in the crystal structure. Both complexes crystallise in the presence of Co(2+), Ba(2+) and Na(+) ions. They reveal at least two different types of coordination environments: (1) specific sites for Co(2+) interacting with N7 of guanine; (2) a central ionic site formed by four phosphate groups, which can be occupied by different ions. One more ionic site that is not always occupied by ions is also visible in the electron density map. All of them play a role in the crystal structure.

Intercalative DNA binding of the marine anticancer drug variolin B

“…1b). As in previously reported isomorphous structures including Co 2+ ions1415161718, the strands at both ends of the DNA duplex are distorted and interact with symmetry-related DNA molecules. At one end cytosine C1 is disordered and the complementary guanine G12 is lying in the minor groove of a neighboring duplex.…”

“…The insertion of the drug is aided by the formation of a hydrogen bond between one of the NH2 groups of variolin B and the G6 phosphate. As a result of the rearrangement, the N7 atoms of guanines G6 and G8 are no longer able to interact with Co 2+ ions17, which would probably impair the formation of the observed multi-stranded DNA structure.…”

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)2 molecules by a bis(9-aminoacridine-4-carboxamide) derivative

“…Although the ligand linker was long enough to allow classical bis-intercalation, the compound instead bound to a novel quadruplex-like intercalation cavity formed by exchange of bases between different duplexes in the junction. Several similar structures, all determined using crystals grown in the presence of Co 2+ ions, have been obtained with mono-intercalators bound (20–24). Although the positive charge of the bound ligands may be important in allowing the juxtaposition of phosphate groups, this ability is clearly not specific to bis-intercalators, and the Co 2+ ions, identifiable in the electron density maps, appear to play a crucial role in stabilizing this structure.…”

Structure of a stacked anthraquinone–DNA complex

“…As a result, their B factors (Table 1) are significantly smaller. It should also be noted that the exact position of a related anthraquinone drug studied at much higher resolution could not be accurately modelled (Valls et al, 2005).…”

“…a standard intercalation. In contrast, anthraquinones with two side chains show unusual stacking features and significant disorder (Yang et al, 2000;Valls et al, 2005).…”