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Title: Interrogating a range of biological targets using chemical biology
Author: Grieves, Thomas
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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Chemical biology uses the tools of chemistry in order to study and better understand biological systems. Techniques such as synthetic chemistry have proved invaluable in the discovery of novel medicines to treat a host of conditions. Polymer chemistry has already provided large numbers of synthetic materials with wildly varying physical and mechanical properties which are useful in every facet of day-to-day life. However, the need for further innovation still remains. Fewer and fewer new medicines make it into clinical use every year as discovery of genuinely novel treatments becomes more difficult and regulatory approval becomes more and more difficult to obtain. The ubiquity of synthetic polymers inevitably results in large amounts waste products which were often useful in the first place because of their exceptional stability. This work describes the application of chemical biology techniques to the process of drug discovery and also to the development of biodegradable packaging materials. High serum cholesterol levels are a major cause of atherosclerosis which in turn is a major cause of heart disease. Ischemic heart disease is the number one cause of death worldwide. Cholesterol lowering drugs, known as statins, are strongly associated in a reduction of mortality rates from heart disease. A library of novel statin compounds was screened for its ability to inhibit HMG-CoA reductase. Several of these compounds showed in vitro activity at least as good as the existing best in class drugs and may also display a novel mode of HMG-CoA reductase binding. The rise of antibiotic resistance is a major concern and the need for novel antibacterial drugs has become critical. A number of novel fluoroquinolone compounds were screened for their antibacterial properties. None of these compounds showed activity in vitro although their structures may function as prodrugs in vivo. The sachet market provides an opportunity for low earners in developing countries to afford detergents and toiletries. Poor waste disposal infrastructures mean that waste sachets have become a major environmental concern. The possibility of producing a biodegradable shampoo sachet using existing commercially available materials was investigated. A novel, ‘bilayer’ approach proved unsuccessful due to limitations in the cellulose and polyvinyl alcohol materials used. A simpler approach using a type of polyhydroxyalkanoate was also unsuccessful. While several biodegradable polymers are currently available, all have limitations to their use as packaging materials particularly when storing liquids.
Supervisor: Hornby, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available