African sleeping sickness, leishmaniasis and Chagas disease are all examples of orphan diseases, so named for the overall lack of attention given to them by major pharmaceutical companies. The infectious agent of the disease is Trypanosoma cruzi. Between 8 to 11 million people in Mexico, Central America, and South America are estimated to have Chagas disease, most of whom do not know they are infected. If untreated, infection is lifelong and can be life threatening.
Recently, the Plakortis species have proven to be a rich source of bioactive cycloperoxides - broadly classified as ‘Plakortides’ - which are reportedly highly selective against T. cruzi. This research proposal aims to answer the following questions: 1) Can the enantioselective peroxidation of unsaturated aldehydes be developed and applied to a synthesis of the Plakortides? 2) Can high potency analogues be synthesised through modification of the olefinic side chain? 3) Will stabilisation of radical metabolites lead to novel analogues with superior activity as potential therapies?
In this project, the fellow will lead a ‘state of the art’, multidisciplinary research programme in a world class European research environment and host. The fellow will develop novel methods in organocatalysis for preparing chiral cycloperoxides, which will be applied to the complex natural products. In turn, this methodology will facilitate the production of aromatic analogues of Plakortide and potentially effective treatments for Chagas disease.
Included in the fellowhip is an extensive training programme incorporating many career-enhancing modules and elements. A joint collaboration will run between Irish and UK universites with the fellow visiting both laboratories where he can broaden his skills from chemistry into biology and biochemistry. The project, therefore, represents an excellent opportunity for a talented fellow with ‘transfer of knowledge’ placed at its core.
Field of science
- /natural sciences/chemical sciences/organic chemistry/aldehydes
- /medical and health sciences/clinical medicine/psychiatry/sleep disorders
Call for proposal
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