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Rational Design of DNA Minor Groove-Binding Anti-Tumor Drugs

  • Richard E. Dickerson
  • Philip Pjura
  • Mary L. Kopka
  • David Goodsell
  • Chun Yoon
Part of the NATO ASI Series book series (NSSA, volume 126)

Abstract

Many of the most useful antitumor drugs act by binding directly to double-helical DNA, interfering with both replication and transcription. Some of these drugs intercalate between adjacent base pairs. A second important class consists of those that bind within the minor groove of B-DNA. These latter tend to show a sequence specificity, binding best to regions of several successive A.T base pairs. We have embarked on a planned course of study of the molecular structures of complexes of such groove-binding drugs with synthetic DNA oligomers, with two goals: to understand the basis for sequence specificity, and to design new drug analogues that are capable of binding specifically to any desired base sequence. Such sequencereading molecules should be capable of being directed against key sequences typical of neoplastic rather than normal cells, or invader rather than host cells. If such molecules become a reality, they should have considerable importance in chemotherapy, directing their action against targeted cells and avoiding some of the more unpleasant side effects associated with chemotherapy.

Keywords

Minor Groove Piperazine Ring Unpleasant Side Effect Bifurcate Hydrogen Bond Adjacent Base Pair 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Richard E. Dickerson
    • 1
  • Philip Pjura
    • 1
  • Mary L. Kopka
    • 1
  • David Goodsell
    • 1
  • Chun Yoon
    • 1
  1. 1.Molecular Biology InstituteUniversity of California at Los AngelesLos AngelesUSA

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