Reduction of electron deficient guanine radical species in plasmid DNA by tyrosine derivatives

Abstract

Guanine bases are the most easily oxidized sites in DNA and therefore electron deficient guanine radical species are major intermediates in the direct effect of ionizing radiation (ionization of the DNA itself) on DNA as a consequence of hole migration to guanine. As a model for this process we have used gamma-irradiation in the presence of thiocyanate ions to generate single electron oxidized guanine radicals in a plasmid target in aqueous solution. The stable species formed from these radicals can be detected and quantified by the formation of strand breaks in the plasmid after a post-irradiation incubation using a suitable enzyme. If a tyrosine derivative is also present during irradiation, the production of guanine oxidation products is decreased by electron transfer from tyrosine to the intermediate guanyl radical species. By using cationic tyrosine containing ligands we are able to observe this process when the tyrosine is electrostatically bound to the plasmid. The driving force dependence of this reaction was determined by comparing the reactivity of tyrosine with its 3-nitro analog. The results imply that the electron transfer reaction is coupled to a proton transfer. The experimental conditions used in this model system provide a reasonable approximation to those involved in the radioprotection of DNA by tightly bound proteins in chromatin.

Positional Dependence of DNA Hole Transfer Efficiency in Nucleosome Core Particles

“…Model studies showed that the rate constant for dG •+ reduction by tyrosine is >10 6 greater than that for trapping by H 2 O (∼6 × 10 4 s −1 , pH 7). 24,35,36 This suggests that dG •+ reduction by tyrosine within a NCP can compete with deprotonation and hole transfer. 36,37 Hole reduction in DNA by Tyr41 was initially probed by examining the effect of a deuterated buffer on HTE (Figure S12, 13).…”

“…In addition, hole transfer can be suppressed by histone tyrosine residues that rapidly reduce dG •+ . 23,24 Consequently, HTE within a NCP may depend on the location of the DNA over which hole migration occurs with respect to the protein structure, in addition to the DNA sequence.…”

“…Duplex DNA (∼145 base pairs) wraps approximately 1.6–1.7 turns around an octameric core containing two copies of four highly positively charged histone proteins (H2A, H2B, H3, H4). − DNA kinks and stretching within NCPs could affect hole transfer by altering π-stacking. In addition, hole transfer can be suppressed by histone tyrosine residues that rapidly reduce dG •+ . , Consequently, HTE within a NCP may depend on the location of the DNA over which hole migration occurs with respect to the protein structure, in addition to the DNA sequence.…”

Application of cobalt oxide nanostructured modified aluminium electrode for electrocatalytic oxidation of guanine and single-strand DNA

“…This may be due to the fact that guanine is the most easily oxidizable base in DNA due to its lowest potential 47,48 and it also tends to be oxidized to form stable radical cations. 49 The obtained results demonstrated the satisfactory selectivity of the proposed CoOx nanoower-modied Al electrode toward the electrocatalytic oxidation of guanine at a remarkable reduced over-voltage. Thus, the proposed electrode could be a practical sensor for the determination of guanine in an assortment of various common oxidizable species without separation.…”

Synthesis and evaluation of benzochalcogenazole-benzimidazole derivatives as potential DNA-binding radioprotectors

“…13 The candidate transient lesions include guanidine radical cations G + which results in formation of stable products such as 8-oxoguanine. 14 This mode of protection is quite distinct from the indirect mode of radioprotection that is provided by the radioprotector amifostine 5, a prodrug of the corresponding aminothiol, which like many other aminothiols, act principally by hydroxyl radical scavenging. 15 As part of a program aimed at discovering more potent radioprotectors we considered the incorporation of the chalcogens S, Se and Te to replace one or both of the N-H groups in the bisbenzimidazole backbone of 1-4 and related molecules.…”