Development and Application of Novel Receptors for Phosphatidylethanolamine and Pyrophosphate

Abstract

This thesis presents the development of a phospholipid-binding protein database and the design, synthesis, and photophysical characterisation of fluorescent molecular probes for the detection of phosphatidylethanolamine and pyrophosphate. The research is divided into four main chapters. The introductory chapter provides an overview of existing phospholipids and the necessity for selective detection methods. It outlines the theoretical basis of fluorescent probes and photophysics and reviews fluorescent receptors considered for detecting the target analytes. Chapter II details the creation of a database focused on lipid recognition by natural proteins, consolidating information on various phospholipids and their specific or selective protein binders. This database serves as a valuable resource for studying protein-lipid interactions. Chapter III discusses the design and synthesis of small molecules for detecting phosphatidylethanolamine, as well as phosphorylated and non-phosphorylated purine or pyrimidinebased molecules. Utilising the intramolecular indicator displacement (IID) mechanism, these probes interact with analytes through coordinative and hydrogen interactions, modulating fluorescence response. The chapter evaluates the probes' effectiveness in detecting the targeted analytes and explores the use of polarity-sensitive fluorophores. Chapter IV focuses on synthesising and analysing probes for anionic molecules, particularly pyrophosphate and phosphatidylserine. These probes, employing the IID mechanism and coordinative interactions, show increased fluorescence intensity upon binding to the anions. The chapter covers the design, synthesis, and evaluation of these probes' detection capabilities.