Exploiting protein conformational change to optimize adenosine-derived inhibitors of HSP70
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.
|Number of pages||12|
|Journal||Journal of Medicinal Chemistry|
|Early online date||27 Apr 2016|
|Publication status||Published - 26 May 2016|