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Synthesis of substrates and inhibitors for the Ser-Thr protein phosphatases 1 and 2A and their use in kinetic mechanistic and structural studies
Reference
B07992
Principal Investigator / Supervisor
Professor David Gani
Co-Investigators /
Co-Supervisors
Institution
University of Birmingham
Department
School of Chemistry
Funding type
Research
Value (£)
160,554
Status
Completed
Type
Research Grant
Start date
11/08/1997
End date
11/10/2000
Duration
38 months
Abstract
A programme to delineate the kinetics, substrate specificity, mechanism and inhibition of ser- thr protein phosphatases PP1 and PP2A is outlined. Initially we will probe the determinants for inhibition by synthetic nodularins and microcystins, prepared using in-house solution and solid-phase techniques in order to establish inhibitor SARs quickly. A major objective is to identify specific inhibitors which would be valuable biochemical tools in elucidating the role of specific PPs in vivo. A new reliable activity assay based upon 14C-labelled phosphorylated peptides will be used to gain the first quantitative kinetic information on substrate specificity (for each enzyme), allow the binding/debinding order of various species to be determined and allow the chemical mechanism for phosphoryl transfer to be probed.
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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