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.
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