BIOL 467 Study Guide - Final Guide: Cytostasis, Fluorescence, P53
Document Summary
Thus compounds that act downstream in apoptosis pathway, and do not require transcription for activity provide an alternative strategy for targeting cancer cells. Secondly, took the most active compound and synthesized chemical libraries based on the structure-activity relationships between the functional groups: identified two classes of compounds: indolones (compound 2) and carbamates (compound 4) Compound 4 most active in biochemical assays, but compound 2 most potent in cells. Targeting downstream of p53 is important because many cancer cell lines de-activate. In screening the molecules, the first screen was for dev-ase activity which would fluoresce when it was cleaved by caspase 3, and then the second screen was an immunoblot identifying the large subunit of active caspase-3. After the secondary screen they still had 42 compounds that increased caspase-3 processing. So they redid both assays and ended up with only 20 that activated procaspase-3 processing data not shown.
