A novel synthetic approach to tyrosine dimers based on pterin photosensitization

Abstract

[EN] Oxidative damage to proteins leads to a variety of modifications that are markers of pathogenesis. One of the most important modifications is the dityrosine (Tyr(2)) cross-link, resulting from an oxidative covalent bond between two tyrosines (Tyr). An optimized methodology for preparation of pure Tyr(2) is important to investigate in detail its physicochemical properties and reactivity. Pterin (Ptr), the parent and unsubstituted compound of oxidized pterins, is able to photosensitize the cross-linking of free tyrosine (Tyr) and tyrosine residues of peptides and proteins through a photoinduced electron transfer mechanism. We have optimized a simple, one-step photocatalyzed formation of Tyr(2), using Ptr as photocatalyst. Our procedure is carried out in aqueous solutions under UV-A radiation for few minutes. The purification of Tyr(2) is performed by reverse-phase chromatography. The obtained highly pure solution is used to fully characterize the Tyr(2) (exact mass and H-1, H-1-H-1 COSY; DEPT; HSQC and HMBC NMR experiments) and to deeper study its fluorescence properties. (C) 2017 Elsevier Ltd. All rights reserved.