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
Kreizman R
(2009)
Core-shell PbI2@WS2 inorganic nanotubes from capillary wetting.
in Angewandte Chemie (International ed. in English)
Lee Seung Seo
(2011)
Biosynthesis of nucleoside antibiotic tunicamycin proceeds via a unique
exo-glycal intermediate
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Lee SS
(2011)
Mechanistic evidence for a front-side, SNi-type reaction in a retaining glycosyltransferase.
in Nature chemical biology
Lercher L
(2013)
DNA modification under mild conditions by Suzuki-Miyaura cross-coupling for the generation of functional probes.
in Angewandte Chemie (International ed. in English)
Lercher L
(2015)
Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation.
in Nature communications
Li WW
(2011)
Tuning the cavity of cyclodextrins: altered sugar adaptors in protein pores.
in Journal of the American Chemical Society
Lin Y
(2010)
The allylic chalcogen effect in olefin metathesis
in Beilstein Journal of Organic Chemistry
Lin YA
(2009)
Olefin metathesis for site-selective protein modification.
in Chembiochem : a European journal of chemical biology
Lin YA
(2010)
Olefin cross-metathesis on proteins: investigation of allylic chalcogen effects and guiding principles in metathesis partner selection.
in Journal of the American Chemical Society
Lin YA
(2013)
Rapid cross-metathesis for reversible protein modifications via chemical access to Se-allyl-selenocysteine in proteins.
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/ |