Katie M Konigsfeld, Melissa Lee, Sarah M Urata, Joe A Aguilera, Jamie R Milligan
Department of Radiology, University of California at San Diego, La Jolla, California 92093-0610, USA.
International journal of radiation biology 2012 MarElectron deficient guanine radical species are major intermediates produced in DNA by the direct effect of ionizing irradiation. There is evidence that they react with amine groups in closely bound ligands to form covalent crosslinks. Crosslink formation is very poorly characterized in terms of quantitative rate and yield data. We sought to address this issue by using oligo-arginine ligands to model the close association of DNA and its binding proteins in chromatin. Guanine radicals were prepared in plasmid DNA by single electron oxidation. The product distribution derived from them was assayed by strand break formation after four different post-irradiation incubations. We compared the yields of DNA damage produced in the presence of four ligands in which neither, one, or both of the amino and carboxylate termini were blocked with amides. Free carboxylate groups were unreactive. Significantly higher yields of heat labile sites were observed when the amino terminus was unblocked. The rate of the reaction was characterized by diluting the unblocked amino group with its amide blocked derivative. These observations provide a means to develop quantitative estimates for the yields in which these labile sites are formed in chromatin by exposure to ionizing irradiation.
Katie M Konigsfeld, Melissa Lee, Sarah M Urata, Joe A Aguilera, Jamie R Milligan. Free terminal amines in DNA-binding peptides alter the product distribution from guanine radicals produced by single electron oxidation. International journal of radiation biology. 2012 Mar;88(3):230-8
PMID: 22124251
View Full Text