Photosensitized oxidation of tyrosine: protein damage and a novel synthetic approach to tyrosine dimers

DANTOLA, MARIA LAURA

Tampa, florida

Congreso; 2018 Biennial Meeting, American Society for Photobiology; 2018

American Society for photobiology

Pterins belong to a familyof heterocyclic compounds which are widespread in living systems andparticipate in relevant biological functions. In pathological conditions, suchas vitiligo, oxidized pterins accumulate in the white skin patches of patientssuffering this depigmentation disorder. It is known that pterins are able tophotosensitize damage in nucleotides, DNA and amino acids by Type I (electron?transfer) and Type II (singlet oxygen) mechanisms. Proteins, due to theirrelatively high abundance and their ability to bind chromophores are one of thepreferential targets of the photosensitized damaging effects of UV radiation onbiological systems. One ofthe most important modifications is the dityrosine (Tyr2)cross-link, an oxidative covalent bond between two tyrosine (Tyr) residues,which is known to occur in many diseases. Therefore, given the biomedicalramifications of the photosensitizing properties of pterins, we set out toinvestigate the capability of pterin (Ptr), the parent and unsubstituted compound of oxidizedpterins, to photoinducechemical changes in free Tyr, and Tyr residues of Melanocyte StimulatingHormone (a-MSH) andalbumin, under UV-A radiation. In particular, we observed that the process isinitiated by an electron transfer reaction from the Tyr to the triplet exitedstate of Ptr. The photosensitization reaction leads to the oxidation anddimerization of Tyr residues. The last process is responsible for the photo-oligomerizationof albumin, yielding big protein structures. Despite the biomedical importanceof Tyr2, the information of its physicochemical properties andreactivity is limited due to the drawbacks of its synthesis. Based on pterinphotosensitization we developed a method to produce Tyr2 in a moreeconomic, efficient and simple manner.Keywords:photosensitization, tyrosine cross-linking, protein damage, pterin, UV-Aradiation