Award details

Chemical and structural integrity of proteins in the glassy state

Reference	BBS/E/F/00041761
Principal Investigator / Supervisor	Dr Roger Parker
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	144,100
Status	Completed
Type	Institute Project
Start date	20/04/2005
End date	30/10/2009
Duration	54 months

Abstract

The aim of this programme of work is to determine the physical and chemical basis and mechanisms of globular protein stability in the glassy state. From empirically-developed industrial practices, two strategies for achieving stability using glassy states can be identified and from these two hypotheses developed. The first concerns the minimisation of molecular mobility in glassy matrices and the second the additional use of specific interactions in protein-polyelectrolyte complexes to achieve stability. To tackle this multi- and cross-disciplinary problem requires expertise in protein chemistry and the physical chemistry of biopolymer glasses. ModeI proteins have been selected for tractable mass spectrometry (ms) and NMR structural analyses. In order to characterise the chemistry and consequent structural modifications, the reactions of peptides with structural context will be used and their reactions in the glassy state screened using ms and circular dichroism. Molecular mobility in glasses will be characterised through calorimetric measurements of glass transition temperatures and structural relaxation rates and electron paramagnetic resonance (EPR) spin label and probe studies of local and global mobility. NMR structural analysis will be performed on the modification to model peptides and proteins. The conditions under which polyelectrolyte complexation occurs will be characterised and its consequent effect on probe mobility and chemical stability. The overall goal is a model relating chemical and physical stability of proteins to the glassy state. While some aspects of the programme will investigate the type of chemical reactions which can proceed in the glass, there will also be detailed kinetic studies of how glassy matrices affect the reaction at the peptide level (chemical reaction) and protein level (aggregation).

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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