Pterin–Thymidine Adducts: From Their Photochemical Synthesis to Their Photosensitizing Properties

Abstract

Pterin (Ptr) is the model compound of aromatic pterins, which are efficient photosensitizers present in human skin and are able to oxidize biomolecules upon UVA irradiation. Photosensitization involves chemical alteration of a biomolecule as a result of the initial absorption of radiation by another chemical species, the photosensitizer. Under anaerobic conditions, Ptr reacts with thymine (T) to form photoadducts (T-Ptr). In this work, we present a method to prepare and purify T-Ptr adducts, using 2′-deoxythymidine 5′-monophosphate (dTMP) and single stranded oligonucleotide 5′-d(TTTTT)-3′ (dT₅), and investigate their photosensitizing properties. Interestingly, the Ptr moiety, when attached to T, retains its photophysical properties. The adduct dTMP-Ptr, upon excitation, forms singlet and triplet excited states, the latter being capable of transferring energy to dissolved O₂ and generating singlet oxygen, with an efficiency similar to Ptr. In air-equilibrated solutions, both dTMP-Ptr and dT₅-Ptr adducts can photosensitize the oxidation of tryptophan and 2′-deoxyguanosine 5′-monophosphate, two of the main targets of photosensitization in biological systems, with efficiencies close to that of free Ptr. The mechanisms involved in the oxidation of biomolecules can be either type I (electron transfer) or type II (singlet oxygen).