Degradation of tyrosine and tryptophan residues of peptides by type I photosensitized oxidation.
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 from3Ptr⁎to dissolved O2was negligible or minor. Other amino acid residues, such as histidine, might be also affected.
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET. Diagonal 113 y 64, 1900 La Plata, Argentina.
Carolina
C
Castaño
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET. Diagonal 113 y 64, 1900 La Plata, Argentina.
Mariana
M
Vignoni
Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique (IMRCP), UMR 5623-CNRS/UPS, Université Toulouse III (Paul Sabatier), 118, route de Narbonne, F-31062 Toulouse cédex 9, France.
Patricia
P
Vicendo
Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique (IMRCP), UMR 5623-CNRS/UPS, Université Toulouse III (Paul Sabatier), 118, route de Narbonne, F-31062 Toulouse cédex 9, France.
Esther
E
Oliveros
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET. Diagonal 113 y 64, 1900 La Plata, Argentina. Electronic address: athomas@inifta.unlp.edu.ar.
Andrés H
AH
Thomas
D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D017319:Photosensitizing Agents; D014443:Tyrosine; D014364:Tryptophan
Electron transfer; Photosensitization; Pterins; Tyrosine; α-MSH