Creating a Synthetic Platform for Understanding and Exploiting Glycoconjugates
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
The evidence for the importance of carbohydrates in biology is increasing exponentially. Unlike other biomolecules (lipids, proteins, nucleosides) significant expertise is needed in the construction of corresponding glycoconjugate probes used to understand and exploit this biology: for example, no automated oligosaccharide synthesizer to date exists for the construction of all the glycoside linkages. The possible permutations for something as simple as the hexasaccharide structures stretch to greater than 1.05 x 1012 possible combinations. This level of complexity highlights that synthesis of glycoconjugates must be guided by functional design, and cannot simply be achieved through random synthesis of all possible combinations. There are a number of startling and challenging high-risk problems that exist in the field of glycoscience that the Platform would allow us to tackle. The risk is high, the challenges of complexity great (due, in part, to the typical lack of direct genetic control of glycoconjugate synthesis within biology) but the potential rewards are tremendous.
Organisations
Publications
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Lin YA
(2010)
The allylic chalcogen effect in olefin metathesis.
in Beilstein journal of organic chemistry
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Liu F
(2014)
Rationally designed short polyisoprenol-linked PglB substrates for engineered polypeptide and protein N-glycosylation.
in Journal of the American Chemical Society
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Lo Conte M
(2011)
Multi-molecule reaction of serum albumin can occur through thiol-yne coupling.
in Chemical communications (Cambridge, England)
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Lucas R
(2008)
Glycomimetic inhibitors of mycobacterial glycosyltransferases: targeting the TB cell wall.
in Chembiochem : a European journal of chemical biology
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Mayorkas N
(2011)
Carbohydrate hydration: heavy water complexes of a and ß anomers of glucose, galactose, fucose and xylose.
in Physical chemistry chemical physics : PCCP
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Mayorkas N
(2011)
Heavy water hydration of mannose: the anomeric effect in solvation, laid bare
in Chemical Science
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Mimura Y
(2007)
Folding of an MHC class II-restricted tumor antigen controls its antigenicity via MHC-guided processing.
in Proceedings of the National Academy of Sciences of the United States of America
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Monrad R
(2014)
Dissecting the reaction of Phase II metabolites of ibuprofen and other NSAIDS with human plasma protein
in Chem. Sci.
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Nielsen MM
(2011)
Substrate and metal ion promiscuity in mannosylglycerate synthase.
in The Journal of biological chemistry
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Nunes C
(2013)
Inhibition of SnRK1 by metabolites: tissue-dependent effects and cooperative inhibition by glucose 1-phosphate in combination with trehalose 6-phosphate.
in Plant physiology and biochemistry : PPB
Description | This Platform grant allowed us scientific freedom to explore some highly unconventional ideas for how molecules containing sugars (so-called glycoconjugates) might work in nature and might be used in medicine. From this work we have discovered new sugar-based drugs to treat disease (including new classes of antibiotics), new ways of detecting disease at a much earlier stage (e.g. TB or MS) and new ways of understanding how nature handles and builds sugars. |
Exploitation Route | The fundamental discoveries are allowing those interested in applications, such as diagnosing or treating disease to do this based on a better understanding. We too are developing these techniques, in partnership with leading clinicians. |
Sectors | Agriculture Food and Drink Chemicals Environment Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
URL | http://users.ox.ac.uk/~dplb0149/ |
Description | BGD and group members have appeared on the radio, television, (BBD, Channel 5), newspapers and journals (The Times, The Herald, New Scientist) science festivals around the world (Cheltenham, Kent, Edinburgh, Times Lit., Sydney) describing this work. We have given talks in schools to inspire the next generation. The work contributed strongly to industrial growth in the biotech sector worldwide and was cited in the BBSRC Innovator of the Year Finalist Citation 2010 for BGD, for example. BGD talked about this work at the Parliamentary and Scientific Committee. |
First Year Of Impact | 2007 |
Sector | Chemicals,Creative Economy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Cultural Societal Economic Policy & public services |
Description | BBSRC Grouped |
Amount | £508,027 (GBP) |
Funding ID | BB/J009725/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2012 |
End | 12/2014 |
Description | BBSRC Grouped |
Amount | £508,027 (GBP) |
Funding ID | BB/J009725/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2012 |
End | 12/2014 |
Company Name | GlycoForm |
Description | |
Year Established | 2002 |
Impact | Employed >20 people over 10 years and provided a model for how synthetic protein drugs might be constructed and used. The technology for this company has now been used by major US companies. |