Omuralide and Vibralactone: Differences in the Proteasome‐ β‐Lactone‐γ‐Lactam Binding Scaffold Alter Target Preferences

: Despite their structural similarity, the natural products omuralide and vibralactone have different biological targets. While omuralide blocks the chymotryptic activity of the proteasome with an IC50 value of 47 nM, vibralactone does not have any effect at this protease up to a concentration of 1 mM. Activity-based protein profiling in HeLa cells revealed that the major targets of vibralactone are APT1 and APT2.