Photosensitization of biological targets

A photosensitized reaction is a process by which a photochemical or photophysical alteration occurs in one molecular entity as a result of the initial absorption of radiation by another molecular entity called photosensitizer (or simply sensitizer). Solar radiation induces modifications to genomic DNA and is implicated in the induction of human skin cancers. UV radiation is the most mutagenic and carcinogenic component of the solar radiation. UV-B radiation (280-320 nm) damages DNA through the direct excitation of the nucleobases. On the other hand, although nucleobases absorb very weakly above 320 nm, UV-A radiation (320-400 nm) may damage DNA through photosensitized reactions. This indirect action is mediated by a photosensitizer (endogenous or exogenous) which is excited by the UV-A radiation.

The chemical changes in DNA and its components resulting from photosensitized reactions can take place through different mechanisms. Energy transfer from the triplet state of the photosensitizer to pyrimidine bases leads to the formation of pyrimidine dimers. Photosensitized oxidations also contribute to DNA damage induced by UV-A radiation. These processes involve the generation of radicals (type I), e.g., via electron transfer or hydrogen abstraction, and/or the production of singlet molecular oxygen (1O2) (type II). The nucleobases are the preferential DNA substrates of type I oxidation. Although guanine is the main target because of its low ionization potential, adenine is also a target in type I sensitized oxidations, being more reactive than pyrimidine bases. On the other hand, guanine is the only DNA component that significantly reacts with 1O2.

Pteridines can act as photosensitizers through both type I and type II mechanisms. The photosensitizing properties of the parent and unsubstituted compounds, pterin and lumazine, have been studied using DNA, purine nucleotides and eukaryotic cells as targets. The study of the photosensitizing properties of the pterin derivatives present in the skin (7,8-dihydrobiopterin, biopterin, 6-formylpterin and 6-carboxypterin) is under progress. Although the photosensitized damage to DNA is well characterized, much less is known about proteins and very little has been studied on inactivation of enzymes caused by photosensitized processes. Currently, our group is studying the damage to albumin and the inactivation of enzymes photoinduced by pterins.

Related publications
"Degradation of a-melanocyte-stimulating hormone photosensitized by pterin"
C. Castaño, C. Lorente, N. Martins-Froment, E. Oliveros, A. H. Thomas
Organic & Biomolecular Chemistry, en prensa (DOI:10.1039/C4OB00434E).

"Photosensitization of bovine serum albumin by pterin: A mechanistic study"
A. H. Thomas, C. Lorente, K. Roitman, M. M. Morales, M. L. Dántola
Journal of Photochemistry and Photobiology B: Biology, 120, 52-58 (2013).

"Oxidation of tyrosine photoinduced by pterin in aqueous solution"
C. Castaño, M. L. Dántola, E. Oliveros, A. H. Thomas, C. Lorente.
Photochemistry and Photobiology, 89, 1448–1455 (2013).

"Type I photosensitization of 2′-deoxyadenosine 5′-monophosphate (5′-dAMP) by biopterin and its photoproduct formylpterin"
M. P. Serrano, C. D. Borsarelli, A. H. Thomas
Photochemistry and Photobiology, 89, 1456–1462 (2013).

"Tryptophan oxidation photosensitized by pterin"
A. H. Thomas, M. P. Serrano, V. Rahal, P. Vicendo, C. Claparols, E. Oliveros, C. Lorente
Free Radical Biology and Medicine, 63, 467–475 (2013).

"Inactivation of tyrosinase photoinduced by pterin"
M. L. Dántola, A. D. Gojanovich, A. H. Thomas.
Biochemical and Biophysical Research Communications, 424, 568–572 (2012).

"Photosensitizing properties of biopterin and its photoproducts using 2’-deoxyguanosine 5’-monophosphate as an oxidizable target"
M. P. Serrano, C. Lorente, F. E. Morán Vieyra, C. D. Borsarelli, A. H. Thomas.
Physical Chemistry Chemical Physics, 14, 11657–11665 (2012).

"Mechanism of electron transfer processes photoinduced by lumazine"
M. P. Denofrio, M. L. Dántola, P. Vicendo, E. Oliveros, A. H. Thomas, C. Lorente
Photochemical and Photobiological Sciences, 11, 409-417 (2012).

"Mechanism of electron transfer processes photoinduced by lumazine"
M. P. Denofrio, M. L. Dántola, P. Vicendo, E. Oliveros, A. H. Thomas, C. Lorente
Photochemical and Photobiological Sciences, 11, 409-417 (2012).

"Photodynamic effects of pterin on HeLa Cells"
M. P. Denofrio, C. Lorente, T. Breitenbach, S. Hatz, F. M. Cabrerizo, A. H. Thomas, P. R. Ogilby
Photochemistry and Photobiology, 87, 862–866 (2011).

"Electron transfer initiated reactions photoinduced by pterins"
C. Lorente, G. Petroselli, M. L. Dántola, E. Oliveros, A. H. Thomas
Pteridines, 22, 111–119 (2011).

"Oxidation of 2’-deoxyadenosine 5’-monophosphate photoinduced by Lumazine"
M. P. Denofrio, A. H. Thomas, C. Lorente
Journal of Physical Chemistry A, 114, 10944–10950 (2010).

"Electron transfer processes induced by the triplet state of pterins in aqueous solutions"
M. L. Dántola, M. Vignoni, C. González, C. Lorente, P. Vicendo, E. Oliveros, A. H. Thomas
Free Radical Biology & Medicine, 49, 1014–1022 (2010).

"The photosensitizing activity of lumazine using 2’-deoxyguanosine 5’-monophosphate and HeLa cells as targets"
M. P. Denofrio, S. Hatz, C. Lorente, F. M. Cabrerizo, P. R. Ogilby, A. H. Thomas
Photochemical and Photobiological Sciences, 8, 1539-1549 (2009).

"Photosensitization of 2’-deoxyadenosine-5’-monophosphate by pterin"
G. Petroselli, R. Erra-Balsells, F. M. Cabrerizo, C. Lorente, A. L. Capparelli, A. M. Braun, E. Oliveros, A. H. Thomas
Organic & Biomolecular Chemistry, 5, 2792-2799 (2007)

"Oxidation of 2'-deoxyguanosine 5'-monophosphate photoinduced by pterin: type I versus type II mechanism"
G. Petroselli, M. L. Dántola, F. M. Cabrerizo, A. L. Capparelli, C. Lorente, E. Oliveros, A. H. Thomas
Journal of the American Chemical Society, 130, 3001-3011 (2008)

"Photoinduced Cleavage of plasmid DNA in Presence of Pterin"
C. Lorente, A. H. Thomas, L. S. Villata, D. Hozbor, A. Lagares y A. L. Capparelli
Pteridines, 11, 100-105 (2000).