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.
Malinina
Lucy
L
Departament d'Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya, Diagonal 647, E-08028 Barcelona, Spain.
Soler-López
Montserrat
M
Aymamí
Joan
J
Subirana
Juan A
JA
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