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Analogues of diadenosine polyphosphates for in vitro and in vivo studies on FHIT - a candidate tumour suppressor protein
Reference
B08013
Principal Investigator / Supervisor
Professor Michael Blackburn
Co-Investigators /
Co-Supervisors
Institution
University of Sheffield
Department
Chemistry
Funding type
Research
Value (£)
90,523
Status
Completed
Type
Research Grant
Start date
11/08/1997
End date
31/12/1999
Duration
28 months
Abstract
We seek to understand the molecular and cellular basis of the human FHIT gene, whose product is a candidate tumour suppressor protein that binds and slowly hydrolyses diadenosine 5'5-tri- and tetra-phosphates. We shall: (i) prepare non-hydrolysable analogues of diadenosine polyphosphates having C-2 symmetry; (ii) evaluate their binding to and inhibition of Ap3A hydrolysis by cloned FHIT protein; (iii) use kinetic and structural (X-ray and later NMR) data to design improved tight binding analogues; and (iv) synthesise non-ionic derivatives of the best binders to make them cell permeable, slow-releasers of ApnA analogues as agonists/antagonists for intracellular studies in vitro and in vivo (in the Kimmel Cancer Center, PA).
Summary
unavailable
Committee
Closed Committee - Biomolecular Sciences (BMS)
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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