Chemical Modification of 5-Hydroxytryptophan Photoinduced by Endogenous Sensitizers Present in Skin

Damage caused to biological targets through sunlight photosensitized reaction is of paramount importance due to their potential effects on human health. In these processes, a chemical alteration of a biomolecule may occur as a result of the initial radiation absorption by another chemical species called photosensitizer. In this respect, pterins are endogenous photosensitizers able of inducing chemical modifications in DNA, proteins and lipids. These molecules are present in many living organisms and play different biological functions. In humans, aromatic pterins (Pt) accumulate in the depigmentation patches on the skin of patients suffering vitiligo. Interestingly, 5-hydroxytryptophan (5-OH-Trp), a common oxidation product of tryptophan acting as a potential endogenous antioxidant, is also present in the skin under oxidative stress conditions, such as those produced by vitiligo. However, the photochemical interaction between Pt and 5-OH-Trp has not been considered yet. With this background, the goal of the present work is to deepen the knowledge of the capability of Pt to photoinduce damage to 5-OH-Trp. By combining different analytical and spectroscopic techniques, we establish that 5-OH-Trp is damaged by Pt through a photosensitized type I process initiated by an electron transfer from the 5-OH-Trp to the Pt triplet excited state that yield the corresponding radical ions. In air-equilibrated aqueous solution four products were identified, two of which correspond to 5-OH-Trp dimers, while the others are a 5-OH-Trp trimer and a dione, in which the 5-OH-Trp has incorporated an oxygen atom. No consumption of Pt was observed in the presence of O2. However, in the absence of O2, further free-radical reactions lead to the reduction of the photosensitizer, and dimers and trimer were the only 5-OH-Trp-derived products detected. The biomedical implications of the generation of this kind of products, in proteins, are discussed.