BINDING OF EPSTEIN-BARR-VIRUS NUCLEAR ANTIGEN-1 TO DNA - INHIBITION BY DISTAMYCIN AND 2 NOVEL DISTAMYCIN ANALOGS

Modulation of the interaction between cellular or viral transcription factors and target DNA sequences may represent a potential experimenta l strategy to control proliferation of neoplastic cells as well as vir us DNA replication. Distamycin represents a likely candidate to mediat e such modulation by pharmacological means. In order to obtain more de tailed information on structure-activity relationships of these compou nds, we have analysed the effects of distamycin and two distamycin ana logues on the binding of a recombinant protein, the Epstein-Barr virus nuclear antigen 1 (EBNA-1) to its target sequence of Epstein-Barr vir us, containing the 12 bp palindromic consensus TAGCATATGCTA. The seque nce selectivity in the binding of distamycin to DNA was evaluated by f ootprinting experiments, while the effects of distamycins on DNA-prote in interactions was analysed by means of electrophoretic mobility shif t assay. The data presented in this paper suggest that distamycin and its analogues differentially inhibit the interaction between DNA-bindi ng proteins and target DNA sequences.