title: Hole transfer in DNA and photosensitized DNA damage: importance of adenine oxidation.
abstract: Photosensitized DNA damage reactions were investigated for two well-known DNA-damaging photosensitizers (Sens), naphthalimide (NI) and napthaldiimide (NDI), which have similar photophysical properties but differ in their redox properties. NI and NDI derivatives (NIN, NDIN), which have cationic side chains and electrostatically binding to DNA due to favorable electrostatic interactions between the negatively charged phosphate groups of DNA and cationic groups, and NIP and NDIP, which possess phosphate groups and do not bind to DNA, were synthesized. NIN and NDIN can oxidize A and G via their singlet excited state, and NDIP oxidizes A and G via its triplet excited state, whereas NIP oxidizes only G. A combination of laser flash photolysis kinetic studies and quantitative HPLC analyses of photosensitized DNA damage was performed for several DNA sequences in the presence of Sens. NIN, NDIN, and NDIP, which oxidizes A, caused significant DNA damage upon photoirradiation, and DNA damage yield increased with the length of the consecutive A stretch. In contrast, NIP, which oxidizes only G, caused only moderate damage to DNA and showed no preference for the consecutive A sequences. These results clearly demonstrate the importance of A-oxidation, especially in consecutive A sequences, which triggers the rapid hole transfer between A's.
authors.affiliation: The Institute of Scientific and Industrial Research (SANKEN), Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan. kiyohiko@sanken.osaka-u.ac.jp
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Kawai
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Osakada
authors.forename: Mamoru
authors.initials: M
authors.lastname: Fujitsuka
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Majima
mesh_terms: D000042:Absorption; D000225:Adenine / Q000737:chemistry*; D001483:Base Sequence; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D007834:Lasers; D008027:Light; D008956:Models, Chemical; D008969:Molecular Sequence Data; D053644:Naphthalimides / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010782:Photolysis; D017319:Photosensitizing Agents / Q000494:pharmacology
chemical_list: D053644:Naphthalimides; D017319:Photosensitizing Agents; D004247:DNA; D000225:Adenine; D010100:Oxygen