ISOHELICAL ANALYSIS OF DNA GROOVE-BINDING DRUGS
ISOHELICAL ANALYSIS OF DNA GROOVE-BINDING DRUGS
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DOI：
10.1021/jm00155a023
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发表时间：
1986-05-01
影响因子：
7.3
通讯作者：
DICKERSON, RE
中科院分区：
文献类型：
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作者：
GOODSELL, D;DICKERSON, RE
许多抗肿瘤药物和许多致癌物质通过结合在双螺旋DNA的小沟内起作用，干扰复制和转录。其中几种，包括netropsin和偏端霉素，是相当碱基特异性的，仅识别和结合某些碱基序列。奈托洛辛的重复吡咯-酰胺单元，以及DNA染色剂和致癌物Hoechst 33258的重复苯并咪唑单元，都比B DNA中沿着小沟底部的碱基对同步啮合长约20%。我们已经进行了系统的计算机搜索，以寻找可能的重复药物骨架，这些骨架与DNA是等螺旋的，并且还提供了能够阅读和区分A. cntdot的化学基团。T和G. C碱基对。这些异螺旋序列阅读药物聚合物的“isolexins”应该提供靶向合成药物类似物的可能性，特异性针对基因组的一个区域，而不是另一个区域，或针对肿瘤细胞优先于正常细胞。
Many antitumor drugs, and many carcinogens, act by binding within the minor groove of double-helical DNA, interfering with both replication and transcription. Several of these, including netropsin and distamycin, are quite base specific, recognizing and binding only to certain base sequences. The repeating pyrrole-amide unit of netropsin, and the repeated benzimidazole unit of the DNA stain and carcinogen Hoechst 33258, both are approximately 20% too long for synchronous meshing with base pairs along the floor of the minor groove in B DNA. We have carried out a systematic computer search for possible repeating drug backbones that are isohelical with DNA and that also provide chemical groups capable of reading and differentiating between A .cntdot. T and G .cntdot. C base pairs. These isohelical sequence-reading drug polymers of "isolexins" should offer the possibility of targeting synthetic drug analogues specifically against one region of a genome rather than another, or against neoplastic cells in preference to normal cells.