Pterin derivatives are involved in various
biological functions, including enzymatic processes that take place in human skin. Unconjugated oxidized
pterins are efficient
photosensitizers under UV-A irradiation and accumulate in the skin of patients suffering from
vitiligo, a chronic depigmentation disorder. These compounds are able to photoinduce the oxidation of the
peptide α-
melanocyte-stimulating hormone (α-
MSH), which stimulates the production and release of
melanin by melanocytes in skin and hair. In the present work we have used two
peptides in which the amino acid sequence of α-
MSH was mutated to specifically investigate the reactivity of
tryptophan (Trp) and
tyrosine residues (Tyr). The parent compound of oxidized
pterins (Ptr) was used as a model
photosensitizer in aqueous
solution at pH5.5 and was exposed to UV-A radiation, a wavelength range where the
peptides do not absorb. Trp residue yields
N-formylkynurenine and
hydroxytryptophan as oxidized products, whereas the Tyr undergoes dimerization and incorporation of
oxygen atoms. In both cases, the first step of the mechanism involves an electron transfer from the
amino acid to the
photosensitizer triplet excited state, Ptr is not consumed and
hydrogen peroxide (H2O2) is released. The role of
singlet oxygen produced by energy transfer from 3Ptr⁎ to dissolved O2 was negligible or minor. Other
amino acid residues, such as
histidine, might be also affected.