Bisimidazoacridones: 2. Steady-state and Time-resolved Fluorescence Studies of Their Diverse Interactions with DNA

Several bisimidazoacridones (BIA) are potent, selective antineoplastic agents, whereas others have potent anti-human immunodeficiency virus activity. BIA are bifunctional agents that consist of two imidazoacridone (IA) chromophores held together by various linkers. Interaction of BIA with DNA has be...

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Veröffentlicht in:Photochemistry and photobiology 2003-10, Vol.78 (4), p.313-322
Hauptverfasser: Tarasov, S G, Casas-Finet, J R, Cholody, WM, Kosakowska-Cholody, T, Gryczynski, Z K, Michejda, C J
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container_title Photochemistry and photobiology
container_volume 78
creator Tarasov, S G
Casas-Finet, J R
Cholody, WM
Kosakowska-Cholody, T
Gryczynski, Z K
Michejda, C J
description Several bisimidazoacridones (BIA) are potent, selective antineoplastic agents, whereas others have potent anti-human immunodeficiency virus activity. BIA are bifunctional agents that consist of two imidazoacridone (IA) chromophores held together by various linkers. Interaction of BIA with DNA has been postulated to be required for their biological activity. Fluorescence data on free and bound BIA suggest that the binding of BIA and similar drugs to DNA is driven by a transfer of hydrophobic molecules from aqueous media to the more amphiphilic DNA environment. Binding to DNA was sensitive to sequence and depended on the length and rigidity of the linker. Time-resolved fluorescence measurements showed that BIA adopt an extended conformation upon binding and that all of the molecules are tightly associated with DNA. Gel-shift and melting assays indicated that one of the aromatic residues of BIA is intercalated, whereas the other, together with a linker, resides in a groove, probably the minor groove. A continuum of structures may be possible where intercalation and classical minor groove binding are limiting structures. In general, the hypothesis for the mechanism of action of BIA wherein the unintercalated residue, accessible for additional interactions, captures a critical protein involved in repair or transcription, is consistent with this model.
doi_str_mv 10.1043/0031-8655(2003)078(0313:BSATFS)2.0.CO;2
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title Bisimidazoacridones: 2. Steady-state and Time-resolved Fluorescence Studies of Their Diverse Interactions with DNA
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