| 8431447 |
van Houte LP, van Garderen CJ, Patel DJ: The antitumor drug nogalamycin forms two different intercalation complexes with d (GCGT).d (ACGC). Biochemistry. 1993 Feb 16;32(6):1667-74.
The structures of the physical complex of d (GCGT).d (ACGC) with the anthracycline antitumor drug nogalamycin were studied in order to determine the sequence specificity and the drug orientation at the symmetric d (C2G3).d (C6G7) binding site of this oligonucleotide. For this purpose, one- and two-dimensional NMR techniques were used in combination with molecular mechanics and molecular dynamics computations. Analysis of the NMR spectra reveals that nogalamycin forms two different intercalation complexes with d (GCGT).d (ACGC). These complexes are called complex I and complex II and are present in a ratio of 0.45:0.55. In both complexes the nogalamycin is intercalated at the d (C2G3).d (C6G7) sequence with the bicyclic and nogalose sugars residing in the major and minor groove, respectively. This results in a buckling of the flanking base pairs and a doubling of the inter-base-pair distances at the intercalation site. In complex I, the aglycon ring of the drug stacks with the C6-G7 bases, and the sugars are directed to the G1.C8 end; while in the case of complex II the anthraquinone ring system is stacked with C2-G3 bases, and the sugars are pointed to the T4.A5 base pair end. The two nogalamycin-d (GCGT).d (ACGC) structures are stabilized by intra- and intermolecular hydrogen bonds, electrostatic interactions, and van der Waals contacts. Comparison of different nogalamycin-oligonucleotide structures reveals a nogalamycin binding specificity to the 3'-side of the cytosine base in cytosine-purine sequences in double-stranded DNA. |
32(0,1,1,2) |