Acridizinium salts as a novel class of DNA-binding and site-selective DNA-photodamaging chromophores.
It was demonstrated that the interaction of the aminoacridizinium salts 2a-2d with DNA depends on the substitution pattern of the chromophore. Spectrophotometric and fluorometric titrations of the acridizinium salts 2a-2d with natural and synthetic polynucleotides reveal that the degree of interaction of the acridizinium salts 2a-2d with the nucleic acid differs significantly. The binding mode of the dyes with DNA was evaluated by circular dichroism and linear dichroism spectroscopy and compared with the parent system 2c. Whereas the 9-aminoacridizinium (2a) mainly intercalates into DNA, the salts 2b-c show a higher degree of association to the DNA backbone. The intercalated aminoacridizinium 2a caused few strand breaks upon UVA exposure, whereas the salts 2b-2d exhibit relatively efficient DNA-damaging properties. All acridizinium salts showed a sequence-selective strand cleavage for guanine-rich DNA regions.
Ihmels
H
H
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. ihmels@chemie.uni-wuerzburg.de
Faulhaber
K
K
Sturm
C
C
Bringmann
G
G
Messer
K
K
Gabellini
N
N
Vedaldi
D
D
Viola
G
G
D000166:Acridines / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000528:radiation effects; D004249:DNA Damage; D005456:Fluorescent Dyes / Q000737:chemistry; D005470:Fluorometry / Q000379:methods; D006147:Guanine / Q000737:chemistry; D007364:Intercalating Agents; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000528:radiation effects; D010957:Plasmids; D012474:Salmon; D012492:Salts; D017422:Sequence Analysis, DNA; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D019914:Taq Polymerase / Q000378:metabolism; D013737:Testis / Q000737:chemistry; D014466:Ultraviolet Rays / Q000009:adverse effects
D000166:Acridines; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D012492:Salts; D006147:Guanine; D004247:DNA; C427203:calf thymus DNA; D019914:Taq Polymerase