Influence of the peptide bond and the presence of tryptophan on the photogeneration and photochemical properties of dityrosine

Abstract

3,3′-Dityrosine, resulting from the formation of a carbon-carbon bond between two tyrosines (Tyr), is one of the most important modifications of the oxidatively generated damage to proteins. Its formation can induce structural changes in proteins, leading to the loss of their biological function. Interestingly, under UVA radiation, dityrosine can also act as an intrinsic photosensitizer that generates reactive oxygen species and induces chemical modifications in amino acids. Despite the biomedical importance of dityrosine, the information regarding its photosensitized generation and photochemical properties is limited due to the drawbacks inherent to its synthesis. In this work we studied the photosensitized formation of dityrosine, in the absence and presence of tryptophan (Trp), using pterin (Ptr) as endogenous type I sensitizer. Free Tyr and Tyr incorporated into specially designed peptides were used as target molecules. Our results indicate that the efficiency of dimerization is not affected by the presence of the peptide bond. Nonetheless, incorporation of dityrosine into a peptide chain appears to confer a certain degree of protection, making it more resistant to photosensitized degradation. Moreover, we demonstrated that, within a peptide chain, an adjacent Trp residue promotes the photoinduced dimerization of Tyr, likely due to electron transfer from the Tyr residue to the oxidized Trp. This effect is not observed when the two residues are more distant. Additionally, the presence of free Trp or Trp within the same peptide chain enhances the efficiency of the photosensitized degradation of the free and peptide dityrosine, respectively.