CASCADECARBOHYDRATES · Catalytic cascade reactions, generic technology for glycobiology
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-05-01 → 2007-04-30
- EU contribution
- €160,180
- Participants
- 1
- Scheme
- IIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - CASCADECARBOHYDRATES (Catalytic cascade reactions, generic technology for glycobiology)
Attachment of monosaccharides to toxic drugs moderates the toxicity making them more useful and also extending their half-life. Additionally mammals have developed transporter systems to enable sugars to pass through cell membranes and this property can prove very useful in enabling drugs to pass through the blood brain barrier to treat diseases of the brain. This project focussed on developing new catalytic cascade reactions to access novel sugar chemistry and hence provide new tools for addressing important disease targets. Catalytic processes, by employing tiny amounts of transition metals to assemble complex products with minimal waste , deliver valuable 'green' or clean chemical processes. When they are combined with cascade processes their value is multiplied because the cascade allows the assembly of 3, 4, 5,.....n different chemicals in one reactor thus producing only one waste stream , minimising energy inputs and maximising the efficient use of manufacturing plant and operating personnel. The project succeeded in generating many new catalytic cascade processes involving the assembly of three-five different chemical building blocks and examples of these were evaluated against bacterial targets, sugar transporters and the blood brain barrier with encouraging results. The project's success reflects the skill and dedication and enthusiasm of Dr Sakee the Marie Curie Fellow from Thailand.
Data: CORDIS, © European Union
Project objective
Innovative chemical manipulation of carbohydrates has lagged significantly behind advances in glycobiology (the biochemistry of carbohydrates). Moreover, despite the widespread involvement of carbohydrates in the fundamental processes underpinning human an d animal health and their involvement in the growth and maturation of many of the species responsible for human/animal illness, e.g. bacteria, viruses, there has not been a concerted and substantial involvement of major pharmaceutical /animal health companies in the design and discovery of novel carbohydrate based medicines. A major part of the perceived problems of carbohydrate based drugs are poor pharmacokinetics (PK), high molecular weight, and the accompanying reduced potential for tuning" PK and lack o f compliance with Lipinski's rules. Additionally the need for novel bioprobes to facilitate elucidation of the pathways and mechanisms of important carbohydrate mediated processes continues to grow.For example glycolipids and glycoproteins have key cell surface recognition / adhesion functions in important diseases such as obesity, inflammation, cancer, host-microbial interactions, toxin-receptor interactions etc. Advances are being made in these areas but would be greatly assisted by "tunable" multivalent bioprobes. This project proposes novel catalytic cascade chemistry (multiple sequential reactions of 3,4 or more reactants occurring in "one-pot") of carbohydrates, which delivers products with high diversity and molecular complexity and allows incorporation of important biomolecules such as nucleosidesor lipids as well as the small heterocycles (privileged structures) at the heart of modern drugs. The high regio- and stereo selectivity of the proposed cascades and their ability to provide multivalent assemblies makes them ideally suited to deliver both novel bioprobes and smaller potential drug discovery leads and is a powerful factor in "tuning" the PK of the products."
Original text from CORDIS.
Participants
- UNIVERSITY OF LEEDS · LEEDSCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union