DNA double helix destabilizing properties of cyclobisintercaland compoundsand competition with a single strand binding protein

The DNA helix destabilizing activity of a series of cyclobisintercaland com pounds (CBIs) has been evaluated by measuring their ability to displace a P -32-labelled oligonucleotide primer (17-mer) hybridized to the single stran ded DNA of M13. This destabilizing activity appears to be strongly dependen t on the cyclic structure (the linear acyclic references are inactive) and the size of the macrocycle; both features being known to determine the pref erential binding of the compound to ssDNA, Interestingly, CBIs induced the dissociation of the duplex template in a concentration range (0.5-1 mu M) c lose to that required for the destabilizing activity of single stranded DNA binding proteins (SSBs). Therefore competition experiments between CBIs an d an SSB protein (Eco SSB) for binding to a single stranded oligonucleotide target (36-mer) have been performed through gel electrophoresis and nitroc ellulose binding assays and strong inhibitory effects on the formation of t he SSB:36-mer complex have been observed. (C) 2000 Elsevier Science Ltd. Al l rights reserved.