A NEW FOLATE DERIVATIVE WITH AFFINITY TO BIOMEMBRANES AND INTERESTING PHOTOSENSITIZING PROPERTIES

FONSECA, JOSÉ LUIS; SOSA, MARÍA JOSÉ; PETROSELLI GABRIELA; ERRA BALSELLS ROSA; QUINDT MATIAS; BONESI SERGIO; GREER, ALEXANDER; GREER, EDYTA M.; THOMAS ANDRÉS H.; VIGNONI MARIANA

San Pablo

Encuentro; 47th Annual Meeting of the Brazilian Biophysical Society; 2023

Brazilian Biophysical Society

Folates are a large family of naturally occurring compounds that comprise Folic acid (PteGlu), a water-soluble B vitamin (B9) and pteroic acid (Pte), among others. They are composed of a pteridine ring linked through a methylene bridge to a PABA unit, which, in turn, is linked to one or more L-glutamic acid residues. Folates may undergo photooxidative cleavage when exposed to UVA light and oxygen, generating unconjugated pterins which themselves bear enhanced photosensitizing properties. Some important target molecules in a photosensitized process are the phospholipids from the lipid membrane, which can undergo lipid peroxidation. It has been shown that a lipophilic photosensitizer can be more efficient since a contact-dependent pathway would be predominant in the photosensitizing process. We have recently described the synthesis of new lipophilic photosensitizers resulting from pterin derivatives. These lipophilic alkyl compounds have been shown to localize in biomembranes leading to membrane damage upon UVA irradiation. In this work, a new lipophilic folate derivative, namely decyl 4-(((2-amino-4-decyloxypteridin-6-yl)methyl)amino)benzoic acid (bis-decyl-Pte), has been synthesized and bears two alkyl chains, one of them linked to the O4 position of the pterin moiety and the other one linked to PABA carboxylic acid group. We also show the spectroscopic properties and photocleavage of bis-decyl-Pte and compare them to Pte behavior. Moreover, we analyze the interaction of bis-decyl-Pte with lipid membranes and investigate the photosensitized induced lipid peroxidation under UVA irradiation.