Photosensitizing properties of biopterin and its photoproducts using 2’-deoxyguanosine 5’-monophosphate as oxidizable target

MARIANA P. SERRANO; CAROLINA LORENTE; FAUSTINO E. MORÁN VIEYRA; CLAUDIO D. BORSARELLI; ANDRÉS H. THOMAS; SOFÍA B. SOLER

Congreso; XI Encuentro Latinoamericano de Fotoquímica y Fotobiología; 2012

Pterins belong to a family of heterocyclic compounds of nitrogen, they can exist in living systems in different redox states and may be classified, according to this property, into oxidized (or aromatic) and reduced pterins. Within the latter group, 7,8-dihydropterins and 5,6,7,8-tetrahydropterins are the most important because they are involved in the metabolism of aminoacids.[1] On the other hand, oxidized pterins are not present in mammalians under physiological conditions, but they accumulate in the skin of human beings suffering from vitiligo, a depigmentation disorder.[2,3] In particular, the oxidation of 7,8-dihydrobiopterin (H2Bip), likely via a photochemical process [4] leads to the accumulation of biopterin (Bip) in the skin under pathological conditions. In addition, 6-carboxypterin (Cap), a product of Bip photolysis, has been isolated from the affected tissues,indicating that excited states of pterins are photogenerated in vivo. This study was aimed to evaluate the photosensitizing properties of oxidized pterins present in the skin and to elucidate the mechanisms involved in the photosensitized oxidation of purine nucleotides by pterins. To this purpose, steady-state and time-resolved experiments in aqueous solution were performed using Bip, Fop and Cap as photosensitizers and the nucleotide 2’-deoxyguanosine 5’-monophosphate (dGMP) as oxidizable target. This compound is a suitable substrate to investigate the behavior of potential photosensitizers  because, apart from being the main target of photoinduced processes in vivo as part of the DNA molecule, dGMP is highly soluble in water and easily quantified by chromatographic methods.[5]. The three pterin derivatives are able to photosensitize dGMP, being Fop the most efficient sensitizer. The reactions proceed through two competing pathways: (1) electron transfer from dGMP to triplet excited-state of pterins (Type I mechanism) and (2) reaction of dGMP with 1O2 produced by pterins (Type II mechanism). Kinetic analysis revealed that the electron transfer pathway is the main mechanism and the interaction of dGMP with the triplet excited-state of pterins and the formation of the corresponding dGMP radicals were demonstrated by laser flash photolysis experiments.   References [1]   C. A. Nichol, G. K. Smith and D. S. Duch, Annu. Rev. Biochem., 1985, 54, 729-764. [2]   H. Rokos, W. D. Beazley and K. U. Schallreuter, Biochem. Biophys. Res. Commun., 2002, 292, 805–811. [3]   K. U. Schallreuter, J. Moore, J. M. Wood, W. D. Beazley, E. M. Peters, L. K. Marles, S. C. Behrens-Williams, R. Dummer, N. Blau and B. Thöny, J. Invest. Dermatol., 2001, 116, 167–174. [4]   Vignoni, F. M. Cabrerizo, C. Lorente, C. Claparols, E. Oliveros and A. H. Thomas Org. Biomol. Chem., 2010, 8, 800–810. [5]   G. Petroselli, M. L. Dántola, F. M. Cabrerizo, A. L. Capparelli, C. Lorente, E. Oliveros and A. H. Thomas, J. Am. Chem. Soc., 2008, 130, 3001–3011.