Nunn C M, Van Meervelt L, Zhang S D, Moore M H, Kennard O
University Chemical Laboratory, Cambridge, U.K.
J Mol Biol. 1991 Nov 20;222(2):167-77. doi: 10.1016/0022-2836(91)90203-i.
The anticancer drug daunomycin has been co-crystallized with the hexanucleotide duplex sequences d(TGTACA) and d(TGATCA) and single crystal X-ray diffraction studies of these two complexes have been carried out. Structure solution of the d(TGTACA) and d(TGATCA) complexes to 1.6 and 1.7 Angstrom resolution, respectively, shows two daunomycin molecules bound to the DNA hexamer. Binding occurs via intercalation of the drug chromophore at the d(TpG) step, and hydrogen bonding interactions involving the drug, DNA and solvent molecules. The daunomycin sugar is located in the minor groove of the DNA hexamer and is stabilized by hydrogen bonds between the amino group of the sugar and functional groups on the floor of the groove. The amino sugar of the d(TGATCA) duplex interacts directly with the DNA sequence, while in the d(TGTACA) duplex, the interaction is via solvent molecules. Two other complexes d(CGTACG)-daunomycin and d(CGATCG)-daunomycin have previously been structurally characterized. Comparison of the four structures with daunomycin bound to the triplet sequences 5'TGT, 5'TGA, 5'CGT and 5'CGA reveals changes in the conformation of both the DNA hexamer and the daunomycin upon complexation, as well as the hydrogen bonding and van der Waals' interactions.
抗癌药物柔红霉素已与六核苷酸双链序列d(TGTACA)和d(TGATCA)共结晶，并对这两种复合物进行了单晶X射线衍射研究。d(TGTACA)和d(TGATCA)复合物的结构解析分别达到了1.6埃和1.7埃的分辨率，结果显示有两个柔红霉素分子与DNA六聚体结合。结合是通过药物发色团在d(TpG)位点的嵌入以及涉及药物、DNA和溶剂分子的氢键相互作用实现的。柔红霉素糖位于DNA六聚体的小沟中，并通过糖的氨基与沟底官能团之间的氢键得以稳定。d(TGATCA)双链体的氨基糖直接与DNA序列相互作用，而在d(TGTACA)双链体中，这种相互作用是通过溶剂分子介导的。另外两种复合物d(CGTACG)-柔红霉素和d(CGATCG)-柔红霉素此前已进行了结构表征。将这四种柔红霉素与三联体序列5'TGT、5'TGA、5'CGT和5'CGA结合的结构进行比较，揭示了复合物形成时DNA六聚体和柔红霉素构象的变化，以及氢键和范德华相互作用的变化。
