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Fragment-based approaches to the design of candidate drugs that interrupt protein-protein interactions involved in cell regulation. (360G-Wellcome-080083_Z_06_Z)

Structure base drug design and Structural bioinformatics are emerging areas that could help lead drug discovery. The Trust has recently awarded £1,022,854 to Professo'r Sir Tom Blundell and colleagues at University of Cambridge to identify candidate ligands that may advance cancer therapeutics. The applicants plan to extend fragment-based approaches and design novel candidates that interrupt protein-protein interactions exploiting small pockets in protein-protein interfaces, particularly where one component is :a flexible polypeptide that assembles to give a specific structure only in the multiproteiri complex. They are specifically examining the multiprotein complex of human recombinase, Rad51, and the product of the breast cancer associated gene, BRCA2. The applicants plan to screen using X-ray, NMR, mass spectrometry, and other biophysical approaches, together with biochemical and biological assays to select and validate useful ligands. This project could identify drugs that block the BRCA2-RAD51 interaction to sensitise canc~r cells to radiation, DNA cross-linking agents or replication inhibitors, or to directly induce cancer cell death during proliferation. In addition, this project has the potential to validate that protein protein interactions are potentially druggable


28 Apr 2006

Grant details
Amount Awarded 1022854
Applicant Surname Blundell
Approval Committee Technology Transfer Challenge Committee
Award Date 2006-04-28T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Translation Award
Internal ID 080083/Z/06/Z
Lead Applicant Prof Sir Tom Blundell
Other Applicant(s) Prof Christopher Abell, Prof Dame Carol Robinson, Prof Alfonso Martinez-Arias, Prof Luca Pellegrini
Planned Dates: End Date 2010-05-28T00:00:00+00:00
Planned Dates: Start Date 2006-09-29T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
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