Pterine-lysine photoadduct: a candidate for photoalergy

FARÍAS, JESUÁN J.; LIZONDO-ARANDA, PALOMA; THOMAS, ANDRÉS H.; LHIAUBET-VALLET, VIRGINIE; DANTOLA, MARIA LAURA

Congreso; XV Encuentro Latinoamericano de Fotoquímica y Fotobiología (XV ELAFOT)-1st LatASP meeting; 2023

ELAFOT-LatASP

Photoalergy is a photosensibility disorder associated with the ability of the skin to react to the combined effect of drugs and sunlight. It has been attributed to the covalent conjugation of proteins with a photosensitizer, yielding modified macromolecules that can act as antigen provoking the immune system response.[1] While some reported photoallergens are often exogenous compounds, so far are few the known endogenous compounds. Aromatic pterins are endogenous photosensitizers present in human skin under pathological conditions. Under UV-A radiation, are able to photodamage DNA, proteins and its components.[2,3] Recently, we demonstrated that pterin (Ptr) binds covalently to Ubiquitin, yielding a Ptr-Ubiquitin adduct that retains the spectroscopic properties of the free photosensitizer.[4] Mass spectrometry analysis suggests Ptr binds in two sites: Lysine and Histidine. With this background, the goal of the present work is to obtain more information about covalent photobinding of Ptr to protein, using Lysine (Lys) and poly-L-lysine (15,000–30,000 Da) as target molecules, and to gain a deeper insight into the molecular basis of skin photosensitivity mediated by endogenous photosensitizers. For this purpose, Ptr was exposed to UV-A radiation in the presence of free Lys and poly-L-lysine under aerated and deareated conditions. The resulting photoproducts were analyzed by spectrophotometry, spectroscopy, high performance liquid chromatography and mass spectrometry.The results obtained in this work allowed us to confirm the formation of photoadducts between Ptr and Lys residues. While the adduct with poly-L-Lysine retains the spectroscopic properties of Ptr, the product obtained with free aminoacid does not behave like Ptr, suggesting a chemical modification in the photosensitizer structure.References:[1] Montaro, S., et. al. Chem. Med. Chem, 4:1196 (2009)[2] Petroselli, G., et al. J. Am. Chem. Soc., 130:3001 (2008)[3] Reid, L.O., et. al. Biochemistry, 55(34):4777 (2016)[4] Reid, L. O., et. al. Chem. Res. Toxicol., 32:2250 (2019)