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 Mg(2+) ions in the asymmetric unit.
We present the crystal structure of an acridine drug derivatized at carbon 9, [N(alpha)-(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 A(3)) unit cell in space group P2(1)2(1)2(1). The duplexes are organized in layers parallel to the ab plane, with consecutive layers crossing each other at right angles.
Departament d'Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya, Diagonal 647, E-08028 Barcelona, Spain.
Lucy
L
Malinina
Montserrat
M
Soler-López
Joan
J
Aymamí
Juan A
JA
Subirana
D000166:Acridines / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014961:X-Ray Diffraction
D000166:Acridines; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D008274:Magnesium