Guanine is the most common site of oxidative damage in DNA. Here, we used a peptide model system to investigate which redox-active side-chain, tyrosine or tryptophan, serves better as an antioxidant in preventing oxidative DNA damage. The peptide sequence used was (Ala)2R(Ala)2R(Ala)3X(Ala)3R(Ala)2R(Ala)2-NH2, with a quartet of basic residues providing an electrostatic attraction for the DNA.  Oxidation of guanine in double-stranded DNA was effected in our experiments by the flash-quench technique.  In this photochemical method, the intercalator, Ru(phen)2dppz2+[phen = phenanthroline, dppz = dipyridophenazine], is excited with a laser and gives an electron to the quencher, Co(NH3)5Cl2+ . The intercalator takes an electron from guanine, creating the guanine radical. Assaying for damage to pUC19 via a nicking and gel shift assay, both peptides were seen to be effective inhibitors of DNA damage.  In transient absorption spectroscopy experiments, guanine radicals are reduced by both peptides on the microsecond timescale, but there appears to be a higher yield of the long-lived tyrosine radical. <br/>

Oxidative DNA damage prevention via tyrosine and tryptophan in a peptide model system

2019 Spring National Meeting

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