Award details

In vitro studies of the interactions of Congo red and analogues with the prion protein: correlations with therapeutic and prophylactic value.

Reference	BBS/E/I/00000777
Principal Investigator / Supervisor	Dr James Hope
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	23,370
Status	Completed
Type	Institute Project
Start date	03/04/2000
End date	02/04/2003
Duration	36 months

Abstract

Transmissible spongiform encephalopathies (TSEs or prion diseases) are rare, progressive disorders of humans and animals. They are invariably fatal with a protracted often asymptomatic time course which can last months or even years. There is no cure for the TSEs and this is of particular concern in Europe where a cross-species transmission of scrapie, the sheep TSE, to cattle has produced bovine spongiform encephalopathy (BSE) and a novel human variant (nvCJD). This has stimulated an intense search for prophylactic or therapeutic drugs which are effective against these infectious disease agents. One compound with anti-prion activity in vivo and in vitro is Congo Red (CR), a sulphonated, azo dye, and we are currently constructing a structure-activity profile of the anti- prion effects of this dye based on the inhibition of PrPres, a molecular marker of the infectious TSE agent in infected cells. Our current experimental approach is as follows : 1. Development of in vitro screening procedures for anti-TSE drugs based on the inhibition of conversion of recombinant PrP to PrPres 2. Mutational analysis of PrP to identify key residues in the conversion assay, and those residues involved in drug binding 3. Characterisation of drug:PrP complexes by biophysical methods; analytical ultracentrifugation, spectroscopy, mass spectrometry, MARS and SPR This project involves close interactions with our current collaborators (School of Pharmacy, University of Cardiff) and the Institute of Biotechnology, Cambridge; centres of excellence in drug development and IP transfer to the biotechnology industry.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
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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