Synthesis of chemical probes targeting membrane proteins
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REID, GERARD, Synthesis of chemical probes targeting membrane proteins, Trinity College Dublin.School of Biochemistry & Immunology, 2019Download Item:
Abstract:
Membrane proteins carry out important physiological functions, including roles as enzymes and receptors, and are the targets for 50% of current drugs on the market,1 indicating their pharmacological importance. Knowledge of the structure and function of membrane proteins is essential in the development of effective therapeutics by structure-based drug design. This project involves the synthesis and characterisation of chemical probes to facilitate structure and function studies on membrane proteins in the Membrane Structural & Functional Biology research group. This project can be divided in three parts; firstly, due to the emerging threat of antibiotic resistance, replenishing the antibiotic development pipeline is of paramount importance. The Membrane Structural & Functional Biology research group has identified the bacterial enzymes lipoprotein diacylglyceryl transferase (Lgt) and apolipoprotein N-acyl transferase (Lnt), as possible targets for new antibiotics. In this work, a number of chromophore labelled phospholipids were synthesised to support the development of a continuous F?rster Resonance Energy Transfer assay for both lipoprotein diacylglyceryl transferase and apolipoprotein N-acyl transferase. Such a high-throughput assay could be used to identify inhibitors. Secondly, a monoacylglycerol that is used in the in meso method for membrane protein crystallisation was synthesised. In addition, the isomerisation of monoacylglycerols that are used in the in meso method and the effect of monoacylglycerol isomerisation on membrane protein crystallisation was studied. Thirdly, synthetic efforts towards unnatural sulfur and selenium containing tryptophan derivatives were carried out in order to facilitate the determination of membrane protein structures.
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Author: REID, GERARD
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Trinity College Dublin. School of Biochemistry & Immunology. Discipline of BiochemistryType of material:
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