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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Parry AL
(2013)
'Multicopy multivalent' glycopolymer-stabilized gold nanoparticles as potential synthetic cancer vaccines.
in Journal of the American Chemical Society
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Parry Alison L.
(2009)
Glycopolymer-functionalized gold nanoparticles: A new strategy toward synthetic anticancer vaccines
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
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Pasparakis G
(2010)
Controlled polymer synthesis--from biomimicry towards synthetic biology.
in Chemical Society reviews
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Patel MK
(2013)
Control of phosphoryl migratory transesterifications allows regioselecive access to sugar phosphates.
in Organic letters
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Patel MK
(2010)
Analysis of the dispersity in carbohydrate loading of synthetic glycoproteins using MALDI-TOF mass spectrometry.
in Chemical communications (Cambridge, England)
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Patel MK
(2010)
Flow chemistry kinetic studies reveal reaction conditions for ready access to unsymmetrical trehalose analogues.
in Organic & biomolecular chemistry
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Patel SM
(2011)
High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity.
in Chemical communications (Cambridge, England)
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Perez-Balderas F
(2017)
Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.
in Nature communications
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Pincu M
(2011)
Isotopic hydration of cellobiose: vibrational spectroscopy and dynamical simulations.
in The journal of physical chemistry. A
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Pérez-Victoria I
(2009)
Saturation transfer difference NMR reveals functionally essential kinetic differences for a sugar-binding repressor protein.
in Chemical communications (Cambridge, England)
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. |