Oxford Glycobiology
Institute
Current Research Programs
- Structural Glycobiology
Dr David J. Harvey, MSc, PhD, DSc,
CChem, FRSC - contact details
Reader, Oxford Glycobiology Institute
Dr Mark R. Wormald, MA (Oxon), D.Phil.,
CChem, MRSC - contact details
University Research Lecturer, Tutor
in Chemistry and Biochemistry at Corpus Christi College
Postdocs :
Dr Andre J. Petrescu (also at Institute of Biochemistry,
Bucharest, Romania)
Graduate students :
Miss Victoria Hunnam
Mr Christopher Lawless
Mr Mukram Mackeen
The function of the Group is to
provide a structural basis, at the molecular level, for the biochemical and
biological research projects being carried out in the Institute.The main
activities of the Group are;
- direct structural analysis,
by NMR spectroscopy and mass spectrometry, of oligosaccharides and related
compounds (for example glycosylated alkaloids or synthetic glycosidase inhibitors).
- characterisation of the conformational,
dynamic and physico-chemical properties of biologically important oligosaccharides,
glycopeptides and glycoproteins by NMR spectroscopy.
- use of computer based molecular
modelling to aid with experimental data interpretation (either from biological
or structural studies) and to provide a structural basis to discuss biochemical
and biological results.
In order to facilitate these studies,
new mass spectrometry based analysis techniques are also being developed
and optimised. The facilities available include; a Finnigan LaserMat 2000,
a VG AutoSpec QFPD mass spectrometers, a Micromass TofSpec 2E MALDI reflectron-TOF
mass spectrometer, a Micromass Q-Tof electrospray mass spectrometer interfaced
to a Waters Cap-LC liquid chromatography system, a Varian UNITY Inova 500
NMR spectrometer and a Silicon Graphics Indigo 2 workstation. Most of the
problems that we work on are generated either by other groups within the
Institute or by external collaborators and currently include;
- identification of the glycans
present on molecules in the immune system - in collaboration with Dr Pauline
Rudd (OGI).
- identification of the glycans
present in the brain - in collaboration with Dr David Wing (OGI).
- identification of plant derived
alkaloids and glycosylated alkaloids - in collaboration with Dr Rob Nash (Institute
of Grassland and Environmental Research, Aberystwyth) and Dr George Fleet
(Dyson Perrins Laboratory, University of Oxford).
- characterisation of synthetic
saccharide mimics with potential as glycosidase or glycosyltransferase inhibitors
- in collaboration with Dr George Fleet (Dyson Perrins Laboratory, University
of Oxford).
- conformational analysis of
glycans involved in chaperone recognition and thus protein folding - in
collaboration with Dr Terry Butters (OGI), Dr Stefana Petrescu (OGI) and
Dr Fran Platt (OGI).
- conformational analysis of
glycopeptides recognised by HLA class 1 molecules - in collaboration with
Ann Glithero (OGI) and Dr Tim Elliott (University of Southampton).
- dynamic properties of immunoglobulin
glycans in relationship to glycan processing and function - in collaboration
with Dr Taj Mattu (OGI).
Selected recent publications :
Sequencing of N-linked oligosaccharides directly from protein gels: In-gel
deglycosylation followed by matrix-assisted laser desorption/ionisation mass
spectrometry and normal-phase high performance liquid chromatography.
B. Kuster, S.F. Wheeler, A.P. Hunter, R.A. Dwek and D.J. Harvey (1997) Anal.
Biochem., 250, 82-101.
The glycosylation of the complement regulatory protein, human erythrocytes
CD59.
P.M. Rudd, B.P. Morgan, M.R. Wormald, D.J. Harvey, C.W. van den Berg, S.J.
Davis, M.A.J. Ferguson and R.A. Dwek (1997) J. Biol. Chem., 272, 7229-7244.
Variations in oligosaccharide-protein interactions in immunoglobulin G
determine the site-specific glycosylation profiles and modulate the dynamic
motion of the Fc oligosaccharides.
M.R. Wormald, P.M. Rudd, D.J. Harvey, S.-C. Chang, I.G. Scragg and R.A.
Dwek (1997) Biochemistry, 36, 1370-1380.
The solution NMR structure of glucosylated N-glycans involved in the early
stages of glycoprotein biosynthesis and folding.
A.J. Petrescu, T.D. Butters, G. Reinkensmeier, S.M. Petrescu, F.M. Platt,
R.A. Dwek and M.R. Wormald (1997) EMBO J., 16, 4302-4310.
Minireview - Glycoproteins: glycan presentation and protein-fold stability.
M.R. Wormald and R.A. Dwek (1999) Structure, 7, R155-R160.
Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates.
D.J. Harvey (1999) Mass Spectrom. Rev., 18, 349-451.
Collision-induced fragmentation of underivatised N-linked carbohydrates
ionized by electrospray.
D. J. Harvey (2000) J. Mass Spectrom., 35, 1178-1190.
Ionization and fragmentation of complex glycans with a Q-TOF mass spectrometer
fitted with a MALDI ion source.
D. J. Harvey, R. H. Bateman, R. S. Bordoli and R. Tyldesley (2000) Rapid
Commun. Mass Spectrom., 14, 2135-2142.