Production and quenching of reactive oxygen species by pterin derivatives, an intriguing class of biomolecules

Abstract

Pterins, a family of heterocyclic compounds derived from 2-aminopteridin-4(1H)-one, are widespread in living systems and participate in important biological functions, such as metabolic redox processes. Under UV-A excitation (320-400 nm), aromatic pterins (Pt) can generate reactive oxygen species (ROS), as a consequence of both energy-and electrontransfer processes from their triplet excited state. Quantum yields of singlet oxygen ( 1 O 2 ) production depend largely on the nature of the substituents on the pterin moiety and on the pH. Formation of the superoxide anion by electron transfer between the pterin radical anion and molecular oxygen leads to the production of significant amounts of hydrogen peroxide (H 2 O 2 ) by disproportionation. Dihydropterins (H 2 Pt) do not produce 1 O 2 but are oxidized by this species with high rate constants yielding pterins as well as H 2 O 2 . In contrast to aromatic derivatives, H 2 Pt are oxidized by H 2 O 2 , and rates and products strongly depend on the nature of the substituents on the H 2 Pt moiety. Aromatic pterins have been found in vivo under pathological conditions, e.g., biopterin or 6-carboxypterin are present in the skin of patients affected by vitiligo, a depigmentation disorder. The biomedical implications of the production of ROS by pterin derivatives and their reactivity with these species are discussed.

Photodynamic inactivation induced by carboxypterin: a novel non-toxic bactericidal strategy against planktonic cells and biofilms ofStaphylococcus aureus

“…Several Ptr derivatives participate in relevant biological processes such as the synthesis of amino acids (Nichol et al 1985) and nucleobases (Blakley 1969), nitric oxide metabolism (Hevel & Marletta 1992) and the activation of cell-mediated immune responses (Fuchs et al 1988). The photochemical behavior of Ptr derivatives in aqueous solution and the consequent formation of ROS have been previously reported (Lorente & Thomas 2006;Oliveros et al 2010). Upon UV-A (320-400 nm) excitation, these compounds form triplet excited states with high quantum yields, and generate organic radicals and ROS.…”

“…Miñán et al in situ by the UV-A excitation of Cap that leads to the formation of its triplet excited state ( 3 Pt*). Previous studies performed with different Ptr derivatives (Oliveros et al 2010;Thomas et al 2013;Castaño et al 2014) demonstrated that three major reaction pathways compete for the deactivation of the triplet excited states of Ptrs: intersystem crossing to the singlet ground state (Reaction 1, see below); energy transfer to O 2 leading to the regeneration of Pt and the production of singlet molecular oxygen ( 1 O 2 ) (Reaction 2); and reaction with an electron donor (Reaction 3), which can be a biological substrate (S) such as proteins, DNA or their components, to form the corresponding pair of radicals (Ptr •-and S •+ ). In the following step, the electron transfer from Pt •-to O 2 regenerates Pt and forms the superoxide anion radical (O 2 •-) (Reaction 4), which undergoes disproportionation into H 2 O 2 and O 2 (Reaction 5).…”

Photosensitization of peptides and proteins by pterin derivatives

“…Pterins are photochemically reactive in aqueous solutions, and upon UV-A excitation, they can fluoresce, produce reactive oxygen species (ROS) [23][24][25] and, as mentioned above, photosensitize the oxidation of biomolecules [8][9][10][11][12][13][14].…”

Chemical changes in bovine serum albumin photoinduced by pterin

“…In the presence of oxygen, pterin (Ptr) [14], the parent and unsubstituted compound of oxidized pterins, acts as a photosensitizer through both type I (electron transfer or hydrogen abstraction) [15] and type II (production of 1 O 2 ) [16] mechanisms. Moreover, Ptr photoinduces DNA damage and the oxidation of purine nucleotides [17][18][19][20].…”