Distamycin analogues with improved sequence-specific DNA binding activities

Alessandra Ciucci, Giordana Feriotto, Carlo Mischiati, Roberto Gambari, Fabio Animati, Paolo Lombardi, Pier Giorgio Natali, Federico Arcamone, Patrizio Giacomini

Research output: Contribution to journalArticlepeer-review


In the present study we have investigated the effect of unprecedented chemical modifications introduced in the distamycin molecule, with the aim of assessing their ability to interfere with sequencespecific DNA-protein interactions in vitro. By using an electrophoretic mobility shift assay, we have been able to identify novel distamycin analogues with improved displacing abilities on the binding of octamer nuclear factors to their target DNA sequence. While variations in the number of pyrrole rings and/or reversion of an internal amide bond result in distamycin-like compounds with identical or very similar properties, the reversion of the formamido into a carboxyamido group or its replacement with the charged formimidoyl moiety significantly improves the ability of the resulting novel distamycin derivatives to compete with OCT-1 (octamer 1 nuclear factor) for its target DNA sequence. Tissue-specific octamer-dependent in vitro transcription is similarly affected by these chemical modifications, suggesting that the ability of distamycins to bind octamer sequences has a direct influence on the functional state of octamer-containing promoters. These data represent an initial, successful attempt to rationalize the design of DNA binding drugs, using distamycins as a model.

Original languageEnglish
Pages (from-to)1583-1591
Number of pages9
JournalBiochemical Pharmacology
Issue number8
Publication statusPublished - Oct 18 1994


  • distamycin
  • electrophoretic mobility shift
  • in vitro transcription
  • nuclear factors
  • octamer

ASJC Scopus subject areas

  • Pharmacology


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