Chelating recombinant antibodies (CRAbs) against bacterial toxins. (360G-Wellcome-075171_Z_04_A)

£13,835

Inhibitors of cGMP-specific phosphodiesterase (PDE5) may be useful for the treatment of cardiovascular diseases such as hypertension. A screen sequence for inhibitors of PDE5 (PDE5i) uses rat models for in vitro and in vivo potency determinations. In order to support their use, the kinetic characteristics and inhibitor sensitivities of human and rat PDE5 were compared. PDE5 was prepared from human and rat platelet cytosol using anion exchange chromatography and enzyme activity determined by monitoring the conversion of [3H]-cGMP to [3H]-5'GMP using scintillation proximity assay. PDE5 was characterised based on substrate specificity, PDE5i sensitivity to UK-343664 and Km for cGMP. The mean apparent Km values (µM), with 95% C.I. (µM), for human pde5 and 4 batches of rat pde5 were 0.54 (0.51, 0.57), 3.1 (1.7, 4.6), 1.7 (0.8, 2.6), 0.8 (0.58, 1.0) and (1.9 (1.1, 2.7) respectively. Rat PDE5 Km values were significantly higher than human PDE5 Km values (P 0.1) that might confound interpretation of functional data obtained using rat models in the PDE5i screen sequence.

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Grant Details

Amount Awarded 13835
Applicant Surname Scott
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2006-02-08T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title PhD Studentship (Basic)
Internal ID 075171/Z/04/A
Lead Applicant Mr Nathan Scott
Partnership Value 13835
Planned Dates: End Date 2008-09-30T00:00:00+00:00
Planned Dates: Start Date 2005-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Martin Allday