Chen K X, Gresh N, Pullman B
Institut de Biologie Physico-Chimique, Laboratoire de Biochimie Théorique associé au CNRS, Paris, France.
Anticancer Drug Des. 1987 Aug;2(1):79-84.
Theoretical computations have been performed on the intercalative binding of anthrapyrazole to the double-stranded tetranucleotides d(GCGC)2 and d(ATAT)2, intercalation taking place in the central pyrimidine-(3',5')-purine sequences, with an unwinding angle of 29 degrees. The complex is principally stabilized by hydrogen-bonds of the two side chains with the ionic oxygens of the two central phosphates. In marked contrast with the corresponding complexes of the related compound mitoxantrone, the N7 atoms of the two central purines do not participate in hydrogen-bonding interactions with the dimethylamino fragments of the side chains. Side chain A of the anthrapyrazole, which is on the imino nitrogen side, is located farther away from the core of the major groove, closer to the phosphate backbone. Compared to the mitoxantrone complexes, there is a considerable decrease in the difference of interaction energy between the d(GCGC)2 and the d(ATAT)2 complexes. This is in line with the experimental results indicating that, compared to mitoxantrone, anthrapyrazole manifests little or no GC sequence selectivity.
已对蒽并吡唑与双链四核苷酸d(GCGC)2和d(ATAT)2的嵌入结合进行了理论计算，嵌入发生在中心嘧啶-(3',5')-嘌呤序列中，解旋角为29度。该复合物主要通过两个侧链与两个中心磷酸酯的离子氧形成的氢键得以稳定。与相关化合物米托蒽醌的相应复合物形成鲜明对比的是，两个中心嘌呤的N7原子不参与与侧链二甲基氨基片段的氢键相互作用。蒽并吡唑位于亚氨基氮一侧的侧链A距离大沟核心较远，更靠近磷酸骨架。与米托蒽醌复合物相比，d(GCGC)2和d(ATAT)2复合物之间相互作用能的差异显著降低。这与实验结果一致，即与米托蒽醌相比，蒽并吡唑几乎没有或没有GC序列选择性。
