DYNAMIC BIS-INTERCALATION OF A HOMODIMERIC THIAZOLE ORANGE-DYE IN DNA- EVIDENCE OF INTERCALATOR CREEPING

We have used one and two dimensional exchange H-1 NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole ora nge dye, ro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodid e (TOTO), to double stranded DNA (dsDNA). The double stranded oligonuc leotides used were d-(CGCTAGCG)(2) ((1) under bar) and d(CGCTAGCTAGCG) (2) ((2) under bar). TOTO binds preferentially to the (5'-CTAG-3')(2) sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with (2) under bar in ratios dependent on the relative amount of TOTO and the o ligonucleotide in the sample. The dynamic exchange between preferentia l binding sites in the case of a 2:1 (1) under bar-TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 (2) under bar-TOTO complex a n intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results dem onstrate the ability of TOTO to migrate along a dsDNA strand in an int ramolecular exchange process. The migration process (''creeping'') alo ng the DNA strand is 6 times faster than the rate of intermolecular ex change between sites in two different oligonucleotides.