Diversity Oriented Synthesis of New Antibacterials

Lead Research Organisation: University of Cambridge
Department Name: Chemistry


The common theme of the research that this fellowship and research grant will support concerns the development of new approaches and techniques to discover biologically active small molecules, such as antibiotics and other drugs. There are two particular aspects of the new approaches that we will concentrate upon: 1. diversity-oriented synthesis, and 2. 3-D small molecule microarraying technology. Diversity-oriented synthesis is a new concept in organic synthesis, where the aim is to synthesise collections of structurally-diverse small molecules efficiently. We will perform a diversity-oriented synthesis to give products with the highest range of structural diversity to date. As 'structural diversity' is somewhat subjective, we will also develop software to analyse collections of small molecules. The compounds that we make will be tested for their ability to kill 'bad' bacteria. 3-D Small molecule microarrays are glass microscope slides (25 x 75 mm) that have thousands of separate polymer spots on the top surface, which contain small molecules at each spot. As each individual spot has a different compound attached to it, they can be used to test all of the small molecules at the same time. This is a highly efficient way of testing so many compounds at once on such a small scale. We will pioneer new methodology in this area to overcome existing problems such as signal-to-noise and surface effects.The fellowship will also allow the completion of other approaches we are researching in synthetic methodology and synthesis of potential new antibiotics, such as the synthesis of lipid A analogues and quorum sensing modulators.


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Robinson A (2008) Gemmacin B: bringing diversity back into focus. in Organic & biomolecular chemistry

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Thomas GL (2008) Anti-MRSA agent discovery using diversity-oriented synthesis. in Angewandte Chemie (International ed. in English)

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Wyatt EE (2006) Skeletal diversity construction via a branching synthetic strategy. in Chemical communications (Cambridge, England)

Description The project contributed to the discovery of two new antibacterial compounds.
Exploitation Route The work has inspired many other groups' research programmes.
Sectors Chemicals

Description In shaping the field of chemistry we are researching, and in the area of drug discovery strategies more broadly.
First Year Of Impact 2011
Sector Chemicals
Impact Types Economic