Applying synthetic organic chemistry in the development of biologically active compounds. Specifically relating to the synthesis of inhibitors of the enzyme nicotinamide N-methyltransferase (NNMT), as well as the development of new antibiotics.
Ned graduated from The University of Glasgow with a 1st class honours MSci degree in chemistry. During his master’s Ned worked under the supervision of Andrew Sutherland on synthesising novel fluorescent benzotriazole derived α-amino acids for use in biological imaging. In 2018 Ned was awarded the prestigious Salters’ Graduate Award by the Salters’ Institute in London after being nominated by the School of Chemistry at the University of Glasgow. Further research experience includes a 12-month placement in 2017 at Procter & Gamble working in an R&D role on detergent technologies. Ned’s contributions to a new product at P&G yielded 6 patents on which he is a named co-inventor.
My research comprises two distinct projects. The first relates to the development of inhibitors of the enzyme nicotinamide N-methyltransferase (NNMT), which includes both the synthesis of potential inhibitors as well as testing their activity. The second focuses on the development of semi-synthetic derivatives of the antibiotic bacitracin that show improved antibiotic activity. NNMT is a cytosolic enzyme that is primarily responsible for the N-methylation of nicotinamide. It is present in a wide variety of human cell types, however is predominantly found in the liver where it plays an important role in the detoxification of xenobiotics. In recent years, NNMT has emerged as a disease-relevant enzyme and has been linked to a variety of different diseases including diabetes, obsesity, Parkinson’s disease and a variety of cancers. Bacitracin is a cyclic peptide metalloantibiotic agent first isolated in 1945 effective against Gram-positive bacteria. Bacitracin binds C55-isoprenyl pyrophosphate, a lipid carrier that shuttles intermediates in cell-wall biosynthesis from the cell’s cytoplasm to its exterior. By interrupting the delivery of peptidoglycan precursors to the location of cell wall synthesis, bacitracin weakens the cell wall and ultimately results in bacterial death. Utilising semisynthetic techniques we hope to improve the antibiotic activity of bacitracin by systematically optimising its structure.
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