Engineering stable calibration standards for biomedical research
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
Work by Davis has demonstrated the feasibility of new manufacturing routines for sitespecificmodification of proteins. This project aims to establish whether these newmanufacturing processes represent a means of manufacturing precise protein calibrationstandard products offering advantages in terms of product specification, stability, processflexibility, economics and scaling. This will find application in enabling first-in-classquantitative immunoassays and standards for mass spectrometry.
Publications
Aljabali A. A. A.
(2014)
Multimeric microparticles of iron oxide (mMPIO) for dual modality molecular imaging with CT & MRI
in EUROPEAN HEART JOURNAL
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
Bernardes GJ
(2011)
Site-selective traceless Staudinger ligation for glycoprotein synthesis reveals scope and limitations.
in Chembiochem : a European journal of chemical biology
Bernardes Goncalo J. L.
(2012)
Chemical site-selective protein modification: Development of a traceless vascular targeting ADC for cancer therapy
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Bernardes Goncalo J. L.
(2012)
Building well-defined glycoproteins
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Boutureira O
(2011)
Direct radiolabelling of proteins at cysteine using [18F]-fluorosugars.
in Chemical communications (Cambridge, England)
Boutureira O
(2012)
Selenenylsulfide-linked homogeneous glycopeptides and glycoproteins: synthesis of human "hepatic Se metabolite A".
in Angewandte Chemie (International ed. in English)
Boutureira Omar
(2012)
Chemical site-selective radiolabelling of proteins using fluorosugars
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Chalker J
(2011)
Methods for converting cysteine to dehydroalanine on peptides and proteins
in Chemical Science
Chalker JM
(2011)
A "tag-and-modify" approach to site-selective protein modification.
in Accounts of chemical research
Chalker JM
(2012)
Conversion of cysteine into dehydroalanine enables access to synthetic histones bearing diverse post-translational modifications.
in Angewandte Chemie (International ed. in English)
Chalker Justin M.
(2011)
Reaction engineering for protein modification
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Chalker Justin M.
(2011)
Allyl sulfides enable olefin metathesis in water and on proteins
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Chalker Justin M.
(2011)
Suzuki-Miyaura cross-coupling on protein substrates using a novel palladium-pyrimidine catalyst
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Chang Y-P
(2014)
DISCOVERY OF A SELECTIVE LYSOSOMAL ALPHA-MANNOSIDASE INHIBITOR FROM AN IMINO-SUGAR LIBRARY
in JOURNAL OF PEPTIDE SCIENCE
Chooi K. Phin
(2014)
Giving p38a kinase a jump-start: p38a Activation induced by chemical modification
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Chooi KP
(2014)
Synthetic phosphorylation of p38a recapitulates protein kinase activity.
in Journal of the American Chemical Society
Cobo I
(2012)
Phosphine-free Suzuki-Miyaura cross-coupling in aqueous media enables access to 2-C-aryl-glycosides.
in Organic letters
Cocinero EJ
(2011)
Sensing the anomeric effect in a solvent-free environment.
in Nature
Cocinero EJ
(2013)
Free fructose is conformationally locked.
in Journal of the American Chemical Society
Cocinero EJ
(2011)
Exploring carbohydrate-peptide interactions in the gas phase: structure and selectivity in complexes of pyranosides with N-acetylphenylalanine methylamide.
in Journal of the American Chemical Society
Cruz IN
(2013)
Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar.
in Chemical science
Dadová J
(2017)
Precise Probing of Residue Roles by Post-Translational ß,?-C,N Aza-Michael Mutagenesis in Enzyme Active Sites.
in ACS central science
Davis Ben
(2012)
Sugars and proteins
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
De Munari S
(2015)
A Triply Divergent Reagent for Glycoprotein Synthesis
in Israel Journal of Chemistry
Dumas A
(2015)
Designing logical codon reassignment - Expanding the chemistry in biology.
in Chemical science
Dumas A
(2013)
Self-liganded Suzuki-Miyaura coupling for site-selective protein PEGylation.
in Angewandte Chemie (International ed. in English)
Díaz-Rodríguez A
(2011)
Chemical modification in the creation of novel biocatalysts.
in Current opinion in chemical biology
Gao Z
(2013)
Enhanced aqueous Suzuki-Miyaura coupling allows site-specific polypeptide 18F-labeling.
in Journal of the American Chemical Society
Goodfellow JJ
(2012)
An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling.
in Journal of the American Chemical Society
Grayson EJ
(2011)
A coordinated synthesis and conjugation strategy for the preparation of homogeneous glycoconjugate vaccine candidates.
in Angewandte Chemie (International ed. in English)
Guimaraes Andreia M. R.
(2011)
Glycosylation enhances selectivity of novobiocin and alters antibacterial mechanism
in ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
Gunnoo SB
(2014)
Creation of a gated antibody as a conditionally functional synthetic protein.
in Nature communications
Howden AJ
(2013)
QuaNCAT: quantitating proteome dynamics in primary cells.
in Nature methods
Kong L
(2013)
Single-molecule interrogation of a bacterial sugar transporter allows the discovery of an extracellular inhibitor.
in Nature chemistry
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
(2015)
Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation.
in Nature communications
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)
Li WW
(2011)
Tuning the cavity of cyclodextrins: altered sugar adaptors in protein pores.
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
Liu F
(2014)
Rationally designed short polyisoprenol-linked PglB substrates for engineered polypeptide and protein N-glycosylation.
in Journal of the American Chemical Society
Lo Conte M
(2011)
Multi-molecule reaction of serum albumin can occur through thiol-yne coupling.
in Chemical communications (Cambridge, England)
Mayorkas N
(2011)
Heavy water hydration of mannose: the anomeric effect in solvation, laid bare
in Chemical Science
| Description | We worked a chemical method for building proteins that act as 'molecular display units'. By using them to display important peptide motifs, we found a way of getting those peptides to be recognised by antibodies. This, in turn, allowed our commercial partners to improve the calibration of their own antibodies, making their products more precise (and hence valuable). In turn, these 'better' calibrated antibodies are allowing more precise and quantitative use of antibodies as widespread 'reagents' in biological science. |
| Exploitation Route | We think that the development of 'better' antibodies will have widespread benefits to improving their use. Beyond that we can envisage using our 'display units' to display all sorts of things in biology, allowing even the design of molecular rulers, for instance. |
| Sectors | Chemicals,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), 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 commercial partners on this work (Badrilla Ltd) have licensed the approach and this increasing their development and growth. |
| First Year Of Impact | 2011 |
| Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Cultural,Societal,Economic |
| 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/ |