Binding of Epstein-Barr virus nuclear antigen 1 to DNA: inhibition by distamycin and two novel distamycin analogues

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

Research output: Contribution to journalArticle

Abstract

Modulation of the interaction between cellular or viral transcription factors and target DNA sequences may represent a potential experimental strategy to control proliferation of neoplastic cells as cell as virus DNA replication. Distamycin represents a likely candidate to mediate such modulation by pharmacological means. In order to obtain more detailed information on structure-activity relationships of these compounds, we have analysed the effects of distamycin and two distamycin analogues on the binding of a recombinant protein, the Epstein-Barr virus nuclear antigen 1 (EBNA-1) to its target sequence of Epstein-Barr virus, containing the 12 bp palindromic consensus TAGCATATGCTA. The sequence selectivity in the binding of distamycin to DNA was evaluated by footprinting experiments, while the effects of distamycins on DNA-protein interactions was analysed by means of electrophoretic mobility shift assay. The data presented in this paper suggest that distamycin and its analogues differentially inhibit the interaction between DNA-binding proteins and target DNA sequences.

Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume267
Issue number2
DOIs
Publication statusPublished - Apr 15 1994

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Keywords

  • DNA-binding drug
  • Epstein-Barr virus
  • Transcription factors

ASJC Scopus subject areas

  • Pharmacology

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