Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A?
A series of anhydride modified cantharidin analogues have been synthesised and screened for their ability to inhibit protein phosphatase 2A. Surprisingly only analogues capable of undergoing a facile ring opening of the anhydride moiety displayed any significant inhibition. Subsequent NMR experiments indicated that 7-oxobicyclo[2.2.1]heptane-2,3-dicarboxylic acid was the major (sole) species under assay conditions. The ability of these modified anhydro-cantharidin analogues to inhibit protein phosphatase 2A varies from 4 (16) to 100% (8) at 100 microM test concentration.
McCuskey
A
A
Keane
M A
MA
Mudgee
L M
LM
Sim
A T
AT
Sakoff
J
J
Quinn
R J
RJ
D000812:Anhydrides / Q000737:chemistry*; D002193:Cantharidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D054648:Protein Phosphatase 2
D000812:Anhydrides; D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D002193:Cantharidin