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

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 well 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