Isohelical analysis of DNA groove-binding drugs.
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 X T and G X C base pairs. These isohelical sequence-reading drug polymers or "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.
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D
Goodsell
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Dickerson
D006690:Bisbenzimidazole / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004214:Distamycins / Q000378:metabolism; D008433:Mathematics; D008958:Models, Molecular; D009429:Netropsin / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D013379:Substrate Specificity
D004214:Distamycins; D009429:Netropsin; C030000:stallimycin; D004247:DNA; D006690:Bisbenzimidazole