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
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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 Alfonso Martinez-Arias, Prof Christopher Abell, Prof Dame Carol Robinson, Prof Luca Pellegrini |
Partnership Value | 1022854 |
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 |