Hydroxyl radical-induced cross-linking of thymine and lysine: identification of the primary structure and mechanism.
Hydroxyl radical-induced formation of a cross-link of thymine (Thy) and lysine (Lys) in the gamma-radiolysis of N2O-saturated aqueous solution was studied. A Thy-Lys cross-link (I) of the formal structure that OH radical and 4-carbon-centered Lys radical added respectively to C(5) and C(6) positions of Thy was isolated by a preparative HPLC and identified by a FAB-HRMS. The primary cross-link I was dehydrated by treatment with HCl at 120 degrees C to yield the secondary structure (II) possessing a C(5)-C(6) double bond in the Thy moiety: the latter structure II was reported previously (Dizdaroglu, M.; Gajewski, E. Cancer Res. 1989, 49, 3463-3467). A pulse radiolysis study with a redox titration method indicated that 4-carbon centered Lys radical intermediate was of neutral redox reactivity in contrast to reducing reactivity of 5-hydroxy-5,6-dihydrothymin-6-yl radical intermediate. The cross-link I could be formed by a conventional radical recombination mechanism, but not by an ionic recombination mechanism involving a redox reaction between the radical intermediates.
Morimoto
S
S
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Japan.
Hatta
H
H
Fujita
S
S
Matsuyama
T
T
Ueno
T
T
Nishimoto
S
S
D003432:Cross-Linking Reagents; D005720:Gamma Rays; D017665:Hydroxyl Radical; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D009609:Nitrous Oxide; D016339:Spectrometry, Mass, Fast Atom Bombardment; D018629:Spectrometry, Mass, Secondary Ion; D013941:Thymine / Q000737:chemistry*
D003432:Cross-Linking Reagents; D017665:Hydroxyl Radical; D008239:Lysine; D009609:Nitrous Oxide; D013941:Thymine