Phospholipid membrane damage produced by photosensitization with decylpterins

MARIANA VIGNONI; ALEXANDER GREER; ROSANGELA ITRI; HELENA C. JUNQUEIRA; MAURÍCIO S. BAPTISTA; MARIA NOEL URRUTIA; ANA REIS; ANDRÉS H. THOMAS

Tampa

Congreso; ASP 2018 Biennial Meeting; 2018

ASP

Oxidative stress to biomembranes occurs in many physiological and pathological processes leading to peroxidation to biomolecules. Key targets include phospholipids bearing polyunsaturated fatty acids (PUFAs), which are abundant compounds of lipid membranes. In addition, PUFAs can undergo photooxidation reactions by the interaction of light, photosensitizer, and oxygen by two different mechanisms: reactions where the generation of radicals takes place (type I mechanism), and reactions where singlet oxygen is produced (type II mechanism). Both mechanisms lead to the generation of hydroperoxides and other oxidation products.Pterins are heterocyclic compounds derived from 2-aminopteridin-4-(3H)-one in biological systems. They accumulate in human skin under pathological conditions. Also, they are photochemically reactive and can act as photosensitizers through both type I and type II mechanisms, inducing damage in proteins and DNA and inactivation of bacteria. Pterin (Ptr) can also photoinduce oxidation of lipids in membranes of large unilamellar vesicles (LUVs). Ptr is a small molecule with low lipophilicity, therefore does not bind to phospholipids and freely crosses biomembranes. We have previously synthesized and characterized a new series of alkyl chain pterin conjugates to increase the lipophilicity of pterins.In this work, we investigated the association of 4-(decyloxy)pteridin-2-amine to lipid membranes and its ability to photoinduce oxidation of phospholipids. The performance of the new decyl-pterin in large or giant unilamellar vesicles of different composition as biomimetic systems was evaluated by analyzing conjugated dienes and the formation of hydroperoxy derivatives using reverse-phase LC-MS detection. Conjugation of a decyl chain in the pterin moiety increases solubility in organic solvents and efficiently intercalate in LUVs. In addition, the decyl-pterins have high singlet oxygen quantum yields. Results were compared to those obtained with Ptr.