研究领域

Bio-organic chemistry

We have a variety of research themes in the area bio-organic chemistry 1. Fluoroquinolone analogs to target Staphylococcus aureus Fluoroquinolone analogs are being synthesized to target increasingly resistant strains of bacteria (specifically S. aureus). We aim to increase the intracellular drug concentration and improve efficacy by overcoming resistance arising from changes to cell permeability and drug efflux. The synthesised analogs are designed to increase efficacy by facilitating active transport through the bacterial cell membranes and preventing efflux. We aim to achieve this by exploiting bacterial uptake mechanisms such as siderophore or glycoside uptake (examples of structures are shown below) examples of structures 2. Design and application of novel analytical constructs to facilitate MS proteome analysis. Since the sequencing of the human genome (identifying the DNA sequences that essentially make us who we are) attention has now turned to the discipline of proteomics which explores the nature and levels of proteins within cells. Although the genome is complex (current estimates suggest the human genome contains around 22,000 genes), the human proteome is vastly more complex, containing around a million proteins. In humans, cellular DNA is constant no matter whether the cell is a brain cell or a heart cell, what makes these cells different is the proteins within the cell (the proteome), whether they are turned on or off. Biologically interesting protein samples tend not only to be highly complex, but often available in only in very limited amounts, so that the dual challenges of sample complexity and limited sample quantities are inherent in proteomic studies. Our research aims to provide chemical tools (proteomic constructs-see below) to facilitate mass spectrometric analysis of peptides resulting from proteolytic digestion of protein samples. proteomic constructs 3. Environmental chemistry (in collaboration with the Food and Environment Research Agency) Perfluorinated compounds (PFCs) have recently emerged as a new class of global environmental pollutants. To date the most studied of these man-made compounds is perfluorooctane sulfonic acid (PFOS), which refers to the individual chemical (C8F17SO3H) (Figure 1) and any closely related derivatives. Our aim is to measure UK exposure and estimate of the overall environmental contamination of PFOS. The role of organic chemistry in this project is to develop novel extraction workflows for PFOS before mass spectrometric measurements

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Greener Solvents for Solid-Phase Synthesis, S. B. Lawrenson, M. North, F. Peigneguy and A. Routledge, Green Chem., 2017, 19, 952–962. Fabrication and Application of Isotopically Labelled Gold Arrays for Multiplexed Peptide Analysis R. Castangia, S.R. Hudson, H.K. Robinson, S.L. Flitsch, J. Thomas-Oates, A. Routledge, ChemBioChem., 2016, 17, 2007-2011. Probing Linker Design in Citric acid-Ciprofloxacin Conjugates, S.J. Milner, A.M. Snelling, K.G. Kerr, A. Abd-El-Aziz, G.H. Thomas, R.E.Hubbard, A. Routledge, A.K.Duhme-Klair, Bioorg. Med. Chem., 2014, 22, 4499-4504.