A trigonal form of the idarubicin:d(CGATCG) complex; crystal and molecular structure at 2.0 Å resolution

Abstract

The X-ray crystal structure of the complex between the anthracycllne Idarublcin and d(CGATCG) has been solved by molecular replacement and refined to a resolution of 2.0 Å. The final R-factor Is 0.19 for 3768 reflections with F0 ≥ 2σ(F0). The complex crystallizes In the trigonal space group P31 with unit cell parameters a = b = 52.996(4), c = 33.065(2)Å, α = β = 90°, γ = 120°. The asymmetric unit consists of two duplexes, each one being complexed with two idarubicln drugs intercalated at the CpG steps, one spermine and 160 water molecules. The molecular packing underlines major groove-major groove interactions between neighbouring helices, and an unusually low value of the occupied fraction of the unit cell due to a large solvent channel of ̃30 Å diameter. This Is the first trigonal crystal form of a DNA-anthracycline complex. The structure is compared with the previously reported structure of the same complex crystallizing In a tetragonal form. The geometry of both the double helices and the Intercalation site are conserved as are the intramolecular interactions despite the different crystal forms. © 1995 Oxford University Press.