A number of advances have been made in the development of modified oligodeoxynucleotides (ODNs), and chemical or physical properties of which are controlled by external stimuli. These intelligent ODNs are promising for the next generation of gene diagnostics and therapy. This paper focuses on the molecular design of artificial ODNs that are activated by X-irradiation and their applications to regulation of hybridization properties, conformation change, radiation-activated DNAzyme, and decoy molecules. 1. Introduction Regulation of chemical or physical properties of oligodeoxynucleotides (ODNs) is important for the development of future gene diagnostics and therapy [1, 2]. Because the function of ODNs is based on their conformation and hybridization properties with their complementary DNA or RNA, various attempts have been made to manipulate these basic characteristics using chemical modification and external stimuli [3–11]. These include the binding of a metal ion to mismatched [3, 4] or modified nucleobases [5, 6], interaction of boron compounds with modified riboses [7, 8], and photochemical methods that use nitrobenzene [9, 10] or azobenzene [11] functionalities on ODNs. High-energy ionizing radiation is an attractive stimulus for controlling the activity of biomaterials, because the radiation reaction can be controlled spatially and temporally without any additives [12, 13]. In particular, X-ray has potential because it has high live-body permeability, and thus, has been extensively used for medical treatment and diagnosis. In this paper, we describe the current state of research on controlling the function of ODNs by X-irradiation. This paper includes our recent research on the development of artificial ODNs possessing a 2-oxoalkyl group [14] or disulfide bonds [15, 16], whose properties and conformation can be regulated by X-irradiation. We applied their characteristics to regulation of hybridization, radiation-activated DNAzyme, regulation of the polymerase reaction, and conformation change of ODNs and decoy molecules for inhibition of protein-DNA interactions. When diluted aqueous solutions are irradiated, practically all of the absorbed energy is deposited in water molecules, and the observed chemical changes are brought about indirectly by the molecular and, in particular, the radical products of water radiolysis. It is well known that ionization and excitation of water molecules by ionizing radiation occur and generate electronically excited states (H2O*), radical cations (H2O+？), and dry electrons ( ). The excited water molecules H2O*
References
[1]
I. Willner, “Photoswitchable biomaterials: en route to optobioelectronic systems,” Accounts of Chemical Research, vol. 30, no. 9, pp. 347–355, 1997.
[2]
J. F. Milligan, M. D. Matteucci, and J. C. Martin, “Current concepts in antisense drug design,” Journal of Medicinal Chemistry, vol. 36, no. 14, pp. 1923–1937, 1993.
[3]
A. Ono and H. Togashi, “Highly selective oligonucleotide-based sensor for mercury(II) in aqueous solutions,” Angewandte Chemie-International Edition, vol. 43, no. 33, pp. 4300–4302, 2004.
[4]
Y. Miyake, H. Togashi, M. Tashiro et al., “ -mediated formation of thymine- -thymine base pairs in DNA duplexes,” Journal of the American Chemical Society, vol. 128, no. 7, pp. 2172–2173, 2006.
[5]
E. Meggers, P. L. Holland, W. B. Tolman, F. E. Romesberg, and P. G. Schultz, “A novel copper-mediated DNA base pair,” Journal of the American Chemical Society, vol. 122, no. 43, pp. 10714–10715, 2000.
[6]
K. Tanaka, A. Tengeiji, T. Kato, N. Toyama, and M. Shionoya, “A discrete self-assembled metal array in artificial DNA,” Science, vol. 299, no. 5610, pp. 1212–1213, 2003.
[7]
T. Wada, N. Minamimoto, Y. Inaki, and Y. Inoue, “Peptide ribonucleic acids (PRNA). 2. A novel strategy for active control of DNA recognition through borate ester formation,” Journal of the American Chemical Society, vol. 122, no. 29, pp. 6900–6910, 2000.
[8]
H. Sato, Y. Hashimoto, T. Wada, and Y. Inoue, “Solid-phase synthesis of peptide ribonucleic acids (PRNA),” Tetrahedron, vol. 59, no. 40, pp. 7871–7878, 2003.
[9]
L. Kr？ck and A. Hechel, “Photoinduced transcription by using temporarily mismatched caged oligonucleotides,” Angewandte Chemie-International Edition, vol. 44, no. 3, pp. 471–473, 2005.
[10]
G. Mayer and A. Hechel, “Biologically active molecules with a “light switch”,” Angewandte Chemie-International Edition, vol. 45, no. 30, pp. 4900–4921, 2006.
[11]
H. Asanuma, T. Ito, T. Yoshida, X. Liang, and M. Komiyama, “Photoregulation of the formation and dissociation of a DNA duplex by using the cis-trans isomerization of azobenzene,” Angewandte Chemie-International Edition, vol. 38, no. 16, pp. 2393–2395, 1999.
[12]
K. Tanabe, Z. Zhang, T. Ito, H. Hatta, and S. I. Nishimoto, “Current molecular design of intelligent drugs and imaging probes targeting tumor-specific microenvironments,” Organic and Biomolecular Chemistry, vol. 5, no. 23, pp. 3745–3757, 2007.
[13]
T. Ito, K. Tanabe, H. Yamada, H. Hatta, and S. I. Nishimoto, “Radiation- and photo-induced activation of 5-fluorouracil prodrugs as a strategy for the selective treatment of solid tumors,” Molecules, vol. 13, no. 10, pp. 2370–2384, 2008.
[14]
K. Tanabe, H. Kanezaki, H. Ishii, and S. I. Nishimoto, “2-Oxoalkyl caged oligonucleotides: one-electron reductive activation into emergence of ordinary hybridization property by hypoxic X-irradiation,” Organic and Biomolecular Chemistry, vol. 5, no. 8, pp. 1242–1246, 2007.
[15]
K. Tanabe, E. Kuraseko, Y. Yamamoto, and S. I. Nishimoto, “One-electron reductive template-directed ligation of oligodeoxynucleotides possessing a disulfide bond,” Journal of the American Chemical Society, vol. 130, no. 20, pp. 6302–6303, 2008.
[16]
K. Tanabe, E. Matsumoto, T. Ito, and S. I. Nishimoto, “Radiolytic cyclization of stem-and-loop structured oligodeoxynucleotide with neighboring arrangement of α,ω-bis-disulfides,” Organic and Biomolecular Chemistry, vol. 8, no. 21, pp. 4837–4842, 2010.
[17]
G. V. Buxton, C. L. Greenstock, W. P. Helman, and A. B. Ross, “Critical review of rate constrants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals in aqueous solution,” Journal of Physical and Chemical Reference Data, vol. 17, no. 2, pp. 513–886, 1988.
[18]
J. W. T. Spinks and R. J. Woods, An Introduction to Radiation Chemistry, Wiley-Interscience, New York, NY, USA, 1990.
[19]
M. Mori, H. Hatta, and S. I. Nishimoto, “Stereoelectronic effect on one-electron reductive release of 5-Fluorouracil from 5-fluoro-1-(2'-oxocycloalkyl)uracils as a new class of radiation-activated antitumor prodrugs,” Journal of Organic Chemistry, vol. 65, no. 15, pp. 4641–4647, 2000.
[20]
Y. Shibamoto, L. Zhou, H. Hatta, M. Mori, and S. I. Nishimoto, “In vivo evaluation of a novel antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), which releases 5-fluorouracil upon hypoxic irradiation,” International Journal of Radiation Oncology Biology Physics, vol. 49, no. 2, pp. 407–413, 2001.
[21]
K. Tanabe, Y. Mimasu, A. Eto et al., “One-electron reduction characteristics of N(3)-substituted 5-fluorodeoxyuridines synthesized as radiation-activated prodrugs,” Bioorganic and Medicinal Chemistry, vol. 11, no. 21, pp. 4551–4556, 2003.
[22]
K. Tanabe, Y. Makimura, Y. Tachi, A. Imagawa-Sato, and S. I. Nishimoto, “Hypoxia-selective activation of 5-fluorodeoxyuridine prodrug possessing indolequinone structure: radiolytic reduction and cytotoxicity characteristics,” Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 9, pp. 2321–2324, 2005.
[23]
J. Li, W. Zheng, A. H. Kwon, and Y. Lu, “In vitro selection and characterization of a highly efficient Zn(II)-dependent RNA-cleaving deoxyribozyme,” Nucleic Acids Research, vol. 28, no. 2, pp. 481–488, 2000.
[24]
A. Yamazawa, X. Liang, H. Asanuma, and M. Komiyama, “Photoregulation of the DNA polymerase reaction by oligunucleotides bearing an azobenzene,” Angewandte Chemie-International Edition, vol. 39, no. 13, pp. 2356–2357, 2000.
[25]
S. Antonello, R. Benassi, G. Gavioli, F. Taddei, and F. Maran, “Theoretical and electrochemical analysis of dissociative electron transfers proceeding through formation of loose radical anion species: reduction of symmetrical and unsymmetrical disulfides,” Journal of the American Chemical Society, vol. 124, no. 25, pp. 7529–7538, 2002.
[26]
M. Z. Hoffman and E. Hayon, “One-electron reduction of the disulfide linkage in aqueous solution. Formation, protonation, and decay kinetics of the RSSR- radical,” Journal of the American Chemical Society, vol. 94, no. 23, pp. 7950–7957, 1972.
[27]
N. K. Mathur, C. K. Narang, and R. E. Williams, Polymers as Aids in Organic Chemistry, Academic Press, New York, NY, USA, 1980.
[28]
M. Ishiguro, SHki no Kagaku Shuushoku, Japan Scientific Societies Press, Tokyo, Japan, 1978.
[29]
A. Wójcik, S. Naumov, B. Marciniak, and O. Brede, “Repair reactions of pyrimidine-derived radicals by aliphatic thiols,” Journal of Physical Chemistry B, vol. 110, no. 25, pp. 12738–12748, 2006.
[30]
S. E. Osborne, J. Volker, S. Y. Stevens, K. J. Breslauer, and G. D. Glick, “Design, synthesis, and analysis of disulfide cross-linked DNA duplexes,” Journal of the American Chemical Society, vol. 118, no. 48, pp. 11993–12003, 1996.
[31]
A. A. Gorodetsky and J. K. Barton, “DNA-mediated electrochemistry of disulfides on graphite,” Journal of the American Chemical Society, vol. 129, no. 19, pp. 6074–6075, 2007.
[32]
M. Endo and T. Majima, “Structural arrangement of two DNA double helices using cross-linked oligonucleotide connectors,” Chemical Communications, no. 11, pp. 1308–1309, 2004.
[33]
G. N. Parkinson, M. P. H. Lee, and S. Neidle, “Crystal structure of parallel quadruplexes from human telomeric DNA,” Nature, vol. 417, no. 6891, pp. 876–880, 2002.
[34]
S. M. Gowan, J. R. Harrison, L. Patterson et al., “A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity,” Molecular Pharmacology, vol. 61, no. 5, pp. 1154–1162, 2002.
[35]
M. Read, R. J. Harrison, B. Romagnoli et al., “Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 9, pp. 4844–4849, 2001.
[36]
M. Nakane, S. Ichikawa, and A. Matsuda, “Triazole-linked dumbbell oligodeoxynucleotides with NF-κB binding ability as potential decoy molecules,” Journal of Organic Chemistry, vol. 73, no. 5, pp. 1842–1851, 2008.
[37]
T. Hosoya, H. Takeuchi, Y. Kanesaka et al., “Sequence-specific inhibition of a transcription factor by circular dumbbell DNA oligonucleotides,” FEBS Letters, vol. 461, no. 3, pp. 136–140, 1999.
