Intercalation of an acridine-peptide drug in an AA/TT base step in the crystal structure of [d(CGCGAATTCGCG)]₂ with six duplexes and seven Mg²⁺ ions in the asymmetric unit

We present the crystal structure of an acridine drug derivatized at carbon 9, [N^α-(9-acridinoyl)-tetraarginine], intercalated within the dodecamer [d(CGCGAATTCGCG)]₂. The presence of a lateral chain at the central carbon 9 atom differentiates this compound from most acridine drugs hitherto studied, which are usually derivatized at carbon 4. The DNA:drug interaction we observe differs from that observed in previous studies, which primarily involves shorter, mainly hexameric sequences, in two important regards: the acridine intercalates within an AA/TT base step, rather than within a CG/CG base step; and the binding site is located at the center of the sequence, rather than at one end of the duplex. In addition, we observe a novel crystal packing arrangement, with six dodecamer duplexes and seven hydrated magnesium ions in the asymmetric unit of a large (66.5 x 68.4 x 77.4 ų) unit cell in space group P2₁2₁2₁. The duplexes are organized in layers parallel to the ab plane, with consecutive layers crossing each other at right angles.