Interaction of alkylated uridines with biological membrane models

• Grant number: 23/12966-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: January 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Luciano Caseli
• Grantee: Guilherme Nuñez Jaroque
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis, AP.TEM
• Associated scholarship(s): 24/19515-5 - Multitechnique Investigation of 3,4-Acetonide-Uridine-Succinate-Cholesterol Interactions with Lipid Mixtures in Membrane Models for Cancer Cells, BE.EP.DR

Abstract

In this project, we intend to study the uridine derivative, 3',4'-acetonide-uridine-succinate-cholesterol (PNM3), which has anticancer drug potential, in membrane models using Langmuir and Langmuir-Blodgett (LB) films of lipids, and complemented with studies on liposomes and through molecular simulation. The lipids to be used will be those found in cell membranes (phosphatidylcholines, phosphatidylglycerols, phosphatidylethanolamines, phosphatidylserines, sphingolipids and sterols), which will be spread at the air-water interface forming Langmuir films. Mixtures with proteins, lipopolysaccharides and peptidoglycans will also be evaluated as components of membrane models. The incorporation of compounds into Langmuir films will be evaluated through pressure and surface potential measurements, adsorption kinetic curves, infrared absorption-reflection spectroscopy (PM-IRRAS), Brewster angle microscopy (BAM), interfacial rheology dilatational and shear. Molecular recognition in the uridine group of PNM3 will be investigated by inserting adenine into the aqueous subphase. b-Diketone complexes of Eu3+ ions such as [Eu(tta)3(H2O)2] will also be co-spread, with the aim of forming nanomaterials with potential applications as luminescent probes. The floating monolayers will be transferred to solid supports using the LB technique and characterized using atomic force microscopy (AFM), fluorescence spectroscopy, PM-IRRAS and quartz crystal microbalance nanogravimetry. In relation to liposomes, the action of the compound incorporated into unilamellar vesicles interacting with Langmuir films will be investigated. The results will be evaluated from the perspective of possible biological implications, inferred from the effects caused by the compound on artificial membranes in search of understanding the mechanism at the molecular level for the prodrug-membrane interaction and the relationships between interactions on biological surfaces between monolayers and lipid bilayers.