© 2008 Oxford University Press
This article appears in the following Nucleic Acid Symposium Series issue: Joint Symposium of the 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids and the 35th International Symposium on Nucleic Acids Chemistry [View the issue table of contents]
Photo-Switched DNA-Binding of a Photochromic Spiropyran
1Department of Chemical and Biological Engineering, Physical Chemistry, Chalmers University of Technology, SE-412 96 Göteborg, Sweden
Abstract
Photochromic molecules, or photochromes, can be reversibly isomerized between two, more or less, thermally stable forms by exposure to light of different wavelengths. Spiropyrans is an important group of photochromes which in their colorless initial state consist of two ring systems connected at a spiro carbon in a closed orthogonal fashion (1c in Scheme 1). Upon irradiation by UV-light, the C-O bond in the pyran ring is broken resulting in the formation of an open planar molecule absorbing in the visible (1o in Scheme 1). Illumination by visible light switches the photochrome back to its initial closed state. Because planar molecules are known to bind to DNA through intercalation, the open form is much more likely to intercalate DNA than the closed isomer. This, together with the fact that interconversion between the two isomers can be controlled by photonic means, enables light controlled DNA-binding. This is a highly novel research area, as the approach in virtually all previous studies aiming at controlling DNA-associated processes by photochromic means has been to covalently link the photochrome to short single-stranded oligonucleotides. Our approach surmounts the need of covalently modifying the targeted DNA molecules, making it much more suitable for any practical biological application.
Scheme 1 Structures of the two isomeric forms of the spiropyran photochrome used in this study.
Here we report the results of DNA-binding studies of spiropyran 1c/1o. Linear dichroism and absorption experiments show that the open form 1o intercalates DNA whereas the closed form 1c shows no or only weak interactions with DNA. Photocycling experiments, where the spiropyran repeatedly has been interconverted between the two isomers in presence of DNA, have shown that it is possible to reversibly control the DNA-binding process using light as external stimuli. We believe that the results from this study could be valuable in the design of future light-activated prodrugs for e.g. cancer treatment.