ENHANCED BINDING OF A HEXACYCLIC AMIDINE ANALOG OF HOECHST-33258 TO THE MINOR-GROOVE OF DNA - H-1-NMR AND UV MELTING STUDIES WITH THE DECAMER DUPLEX D(GGTAATTACC)(2)

NMR and UV melting studies with the decamer duplex d(GGTAATTACC)(2) sh ow that replacing the N-methylpiperazine ring of the DNA minor groove binding agent Hoechst 33258 with a hexacyclic amidine leads to both an increase in duplex stability (Delta T-m approximate to 7 degrees C) a nd enhanced A-T specific recognition; the amidine NH exchanges slowly with the solvent and has a small temperature coefficient (<3 ppb/degre es C) supporting its involvement in intermolecular hydrogen bonding, h owever, the data suggest that the ring is flipping rapidly even at 278 K even though the interaction appears to contribute significantly to complex stability.