Effects of triplex-forming oligonucleotides and DNA-binding drugs on protein/DNA interactions

Sequence-selectivity of DNA-binding drugs and triple helix-forming oligonucleotides (TFO) was recently reported in a number of studies employing footprinting and gel retardation approaches. Among DNA-binding drugs, chromomycin is known to bind to the minor groove of the DNA and to display selectivity for C+G rich regions. In this review we describe the cooperative effects of chromomycin and TFOs recognizing G+C rich Sp1 binding sites. The main conclusion of our paper is that chromomycin potentiates the effects of TFOs in inhibiting the interactions between nuclear proteins and target DNA sequences containing Sp1 binding sites. These data are in agreement with the hypothesis that both DNA-binding drugs and TFOs could be considered as sequence-selective modifiers of DNA/protein interactions, possibly leading to specific alterations of biological functions. Their combined use could be suggested in order to abolish the interactions between promoter-specific transcription factor Sp1 and DNA target sequences.