A novel synthetic approach to tyrosine dimers based on pterin photosensitization

[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.The present work was partially supported by Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET; Grant PIP 0304), Agencia de Promocion Cientifica y Tecnologica (ANPCyT; Grants PICT 2012-0508), and Universidad Nacional de La Plata (UNLP; Grant X586 and X712). L.O.R. and C.C. thanks CONICET for doctoral research fellowships. Funding from the Programa CSIC de Cooperacion Cientifica para el Desarrollo (iCOOPLight project ref 20105CD0017) is gratefully acknowledged. A.H.T. and M.L.D are research members of CONICET. The authors thank Dr. Mariana Vignoni (INIFTA, CONICET) and Nathalie Martins-Froment of the Service Commun de Spectrometrie de Masse (FR2599), Universite de Toulouse III (Paul Sabatier) for their crucial contributions in mass spectrometry measurements.Reid, LO.; Castaño, C.; Dantola, ML.; Lhiaubet ., VL.; Miranda Alonso, MÁ.; Marín García, ML.; Thomas, AH. (2017). A novel synthetic approach to tyrosine dimers based on pterin photosensitization. Dyes and Pigments. 147:67-74. https://doi.org/10.1016/j.dyepig.2017.07.058S677414