MEDI 365 |
| GHKL refers to the protein superfamily that includes DNA gyrase (G), molecular chaperones HSP90 (H), Histidine kinases (K), and DNA Mismatch Repair Enzyme MutL (L). The superfamily is rich in established and proposed drug targets for cancer (H) and bacterial infectious disease (G,L,K). Structural studies revealed the Bergerat fold of the ATP binding domain as the defining feature of the GHKL superfamily. A fragment-based approach was applied to identify small scaffolds (MW < 300) from commercially available compounds to target superfamily-specific regions of the active sites. About 100 compounds were selected and assayed against DNA Gyrase and HSP90. A high percentage showed inhibition, with the best around 100 uM, with ATP competition. Libraries have been designed using these small, robust scaffolds to increase the affinities and fine tune specificity. |
|
General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Medicinal Chemistry |