The reactivity of 2,5-diaminoimidazolone base modification towards aliphatic primary amino derivatives: nucleophilic substitution at C5 as a potential source of abasic sites in oxidatively damaged DNA |
| |
Authors: | Marina Roginskaya Hannah Janson Devanamuni Seneviratni Yuriy Razskazovskiy |
| |
Institution: | 1.Department of Chemistry,East Tennessee State University,Johnson City,USA;2.Department of Physics and Astronomy,East Tennessee State University,Johnson City,USA |
| |
Abstract: | N5-deoxyribosyl derivatives of 2,5-diaminoimidazolone formed by oxidative damage to the guanine bases in 2-deoxyguanosine and highly polymerized DNA readily undergo nucleophilic substitution at C5 in reaction with primary amines in neutral aqueous solutions at 37–70 °C, as it was found in a kinetic study using reverse-phase HPLC. The reaction of 2-amino-5-(2′-deoxy-β-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (dIz) with excess of ethanolamine, alanine and γ-aminobutyric acid (0.2–1 M) is a pseudo-first-order process that proceeds with 45–80 % yields depending on the nature of the amine, its concentration, and the reaction temperature. In the case of ethanolamine, the corresponding bimolecular rate constant has a pre-exponential factor and activation energy of 1.1 × 105 s?1 and 47 kJ mol?1, respectively. The reaction is highly competitive with the previously described hydrolysis of dIz into 2,2-diamino-4-(2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone under biologically relevant conditions. A similar reaction with the same lesion in polymeric DNA results in the release of a low-molecular-weight analog of dIz, presumably producing an abasic site as the second reaction product. Kinetic characteristics of this process make it a potentially important source of abasic sites in oxidatively damaged DNA, formed through the reaction of 2,5-diaminoimidazolone lesions with naturally abundant DNA-affinic amines and proteins. The release of low-molecular-weight analogs of dIz can potentially be employed for quantification of imidazolone lesions in oxidized DNA. The half-life of imidazolone lesions in double-stranded DNA evaluated using this approach was found to be 154 min at 37 °C. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|