STRUCTURAL MODIFICATION CHANGES THE DNA-BINDING MODE OF CATION-SUBSTITUTED ANTHRAQUINONE PHOTONUCLEASES - ASSOCIATION BY INTERCALATION OR MINOR-GROOVE BINDING DETERMINES THE DNA CLEAVAGE EFFICIENCY

The mode of binding anthraquinone derivatives, bearing positively char ged ammonium side chains, to duplex DNA was investigated by optical an d; NMR spectroscopy. Absorption, circular dichroism, emission, and one -and two-dimensional homonuclear NMR spectroscopy show that mono-and d ication-substituted quinones, AQS and 27AQS, bind primarily by interca lation. In contrast, these experiments indicate that the tetracationic anthraquinone 27AQS2 is bound nonintercalatively to duplex DNA. In pa rticular, analysis of the NMR spectrum of 27AQS2 bound to a specially designed synthetic self-complementary dodecanucleotide (5'-CGCGAATTCGC G-3') shows it to be associated primarily with the minor groove of the central AATT sequence. The change in the DNA binding mode greatly aff ects the photophysical and photochemical properties of these photonucl eases with DNA.