title: Peptide repair of oxidative DNA damage.
abstract: Guanyl radical species are produced in DNA by electron removal caused by ionizing radiation, photoionization, oxidation, or photosensitization. DNA guanyl radicals can be reduced by electron donation from mild reducing agents. Important biologically relevant examples are the redox active amino acids cysteine, cystine, methionine, tryptophan, and tyrosine. We have quantified the reactivity of derivatives of these amino acids with guanyl radicals located in plasmid DNA. The radicals were produced by electron removal using the single electron oxidizing agent (SCN)(2)(*)(-). Disulfides (cystine) are unreactive. Thioethers (methionine), thiols (cysteine), and phenols (tyrosine) react with rate constants in the range 10(4)-10(6), 10(5)-10(6), and 10(5)-10(6) dm(3) mol(-1) s(-1), respectively. Indoles (tryptophan) are the most reactive with rate constants of 10(7)-10(8) dm(3) mol(-1) s(-1). Selenium analogues of amino acids are over an order of magnitude more reactive than their sulfur equivalents. Increasing positive charge is associated with a ca. 10-fold increase in reactivity. The results suggest that amino acid residues located close to DNA (for example, in DNA binding proteins such as histones) might participate in the repair of oxidative DNA damage.
authors.affiliation: Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0610, USA. jmilligan@ucsd.edu
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Milligan
authors.forename: Nancy Q
authors.initials: NQ
authors.lastname: Tran
authors.forename: Anne
authors.initials: A
authors.lastname: Ly
authors.forename: John F
authors.initials: JF
authors.lastname: Ward
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D005720:Gamma Rays; D006147:Guanine / Q000737:chemistry / Q000528:radiation effects; D007700:Kinetics; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D010455:Peptides; D006147:Guanine