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
A Celik
(2007)
Direct Biocatalytic Conversion of Carbon Dioxide: Towards a Formic Acid Economy
in in preparation
A Celik
(2007)
Creating new Tools for a Formic Acid Economy: Cloning & Structure of Novel Dehydrogenases
in in preparation
Aljabali A. A. A.
(2014)
Multimeric microparticles of iron oxide (mMPIO) for dual modality molecular imaging with CT & MRI
in EUROPEAN HEART JOURNAL
Allman SA
(2009)
Potent fluoro-oligosaccharide probes of adhesion in Toxoplasmosis.
in Chembiochem : a European journal of chemical biology
Baboo S
(2014)
Most human proteins made in both nucleus and cytoplasm turn over within minutes.
in PloS one
Backus KM
(2014)
The three Mycobacterium tuberculosis antigen 85 isoforms have unique substrates and activities determined by non-active site regions.
in The Journal of biological chemistry
Backus KM
(2011)
Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis.
in Nature chemical biology
Bagi Zsolt
(2013)
Microparticles bearing RGD peptide promote integrin avß3-dependent platelet adhesion in isolated, pressurized cerebral artery
in FASEB JOURNAL
Barry C
(2013)
'Naked' and Hydrated Conformers of the Conserved Core Pentasaccharide of N-linked Glycoproteins and Its Building Blocks
in Journal of the American Chemical Society
Barry CS
(2011)
ESI-MS assay of M. tuberculosis cell wall antigen 85 enzymes permits substrate profiling and design of a mechanism-based inhibitor.
in Journal of the American Chemical Society
| 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 Ltd |
| Description | drug delivery and glycoprotein specialist; biopharmaceuticals |
| 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. |
| Website | http://isis-innovation.com/news/glycoform-ltd-improve-drug-delivery/ |