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 charged ammonium side chains, to duplex DNA was investigated by optical and NMR spectroscopy. Absorption, circular dichroism, emission, and one- and two-dimensional homonuclear NMR spectroscopy show that mono- and dication-substituted quinones, AQS and 27AQS, bind primarily by intercalation. In contrast, these experiments indicate that the tetracationic anthraquinone 27AQS2 is bound nonintercalatively to duplex DNA. In particular, analysis of the NMR spectrum of 27AQS2 bound to a specially designed synthetic self-complementary dodecanucleotide (5'-CGCGAATTCGCG-3') shows it to be associated primarily with the minor groove of the central AATT sequence. The change in the DNA binding mode greatly affects the photophysical and photochemical properties of these photonucleases with DNA.
Breslin
D T
DT
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, USA.
Yu
C
C
Ly
D
D
Schuster
G B
GB
D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D010782:Photolysis; D013053:Spectrophotometry
D000880:Anthraquinones; D002412:Cations; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D004247:DNA