Tunable DNA Photocleavage by an Acridine-Imidazole Conjugate
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- 作者：Beth Wilson ; Lourdes Gude ; Marí ; a-José ; Ferná ; ndez ; Antonio Lorente ; and Kathryn B. Grant
- 刊名：Inorganic Chemistry
- 出版年：2005
- 出版时间：September 5, 2005
- 年：2005
- 卷：44
- 期：18
- 页码：6159 - 6173
- 全文大小：368K
- 年卷期：v.44,no.18(September 5, 2005)
- ISSN：1520-510X
文摘
We report the synthesis and characterization of photonucleases N,N'-bis[2-[bis(1H-imidazol-4-ylmethyl)amino]ethyl]-3,6-acridinediamine (7) and N-[2-[bis(1H-imidazol-4-ylmethyl)amino]ethyl]-3,6-acridinediamine (10), consisting of acentral 3,6-acridinediamine chromophore attached to 4 and 2 metal-coordinating imidazole rings, respectively. InDNA reactions employing 16 metal salts, photocleavage of pUC19 plasmid is markedly enhanced when compound7 is irradiated in the presence of either Hg(II), Fe(III), Cd(II), Zn(II), V(V), or Pb(II) (low-intensity visible light, pH7.0, 22 
C, 8-50 
M 7). We also show that DNA photocleavage by 7 can be modulated by modifying buffer typeand pH. Evidence of metal complex formation is provided by EDTA experiments and by NMR and electrosprayionization mass spectral data. Sodium azide, sodium benzoate, superoxide dismutase, and catalase indicate theinvolvement of type I and II photochemical processes in the metal-assisted DNA photocleavage reactions. Thermalmelting studies show that compound 7 increases the Tm of calf thymus DNA by 10 ± 1 C at pH 7.0 and that theTm is further increased upon the addition of either Hg(II), Cd(II), Zn(II), or Pb(II). In the case of Fe(III) and V(V),a colorimetric assay demonstrates that compound 7 sensitizes one electron photoreduction of these metals toFe(II) and V(IV), likely accelerating the production of type I reactive oxygen species. Our data collectively indicatethat buffer, pH, Hg(II), Fe(III), Cd(II), Zn(II), V(V), Pb(II), and light can be used to "tune" DNA cleavage by compound7 under physiologically relevant conditions. The 3,6-acridinediamine acridine orange has demonstrated great promisefor use as a photosensitizer in photodynamic therapy. In view of the distribution of iron in living cells, compound7 and other metal-binding acridine-based photonucleases should be expected to demonstrate excellent photodynamicaction in vivo.
C, 8-50 M 7). We also show that DNA photocleavage by 7 can be modulated by modifying buffer typeand pH. Evidence of metal complex formation is provided by EDTA experiments and by NMR and electrosprayionization mass spectral data. Sodium azide, sodium benzoate, superoxide dismutase, and catalase indicate theinvolvement of type I and II photochemical processes in the metal-assisted DNA photocleavage reactions. Thermalmelting studies show that compound 7 increases the Tm of calf thymus DNA by 10 ± 1 C at pH 7.0 and that theTm is further increased upon the addition of either Hg(II), Cd(II), Zn(II), or Pb(II). In the case of Fe(III) and V(V),a colorimetric assay demonstrates that compound 7 sensitizes one electron photoreduction of these metals toFe(II) and V(IV), likely accelerating the production of type I reactive oxygen species. Our data collectively indicatethat buffer, pH, Hg(II), Fe(III), Cd(II), Zn(II), V(V), Pb(II), and light can be used to "tune" DNA cleavage by compound7 under physiologically relevant conditions. The 3,6-acridinediamine acridine orange has demonstrated great promisefor use as a photosensitizer in photodynamic therapy. In view of the distribution of iron in living cells, compound7 and other metal-binding acridine-based photonucleases should be expected to demonstrate excellent photodynamicaction in vivo.