2-Carboxymethylendothal analogues as affinity probes for stabilized protein phosphatase 2A Original Research Article

Endothal (diacid) and [3H]cantharidic acid ([3H]CA) bind with high affinity to the catalytic subunit of protein phosphatase 2A (PP2A). PP2A in liver cytosol was greatly stabilized with 30% glycerol as a preliminary step in the potential use of endothal-type derivatives for affinity chromatography. We report here the first introduction of a functionalizable group into endothal which allows retention of binding site affinity (assayed as [3H]CA binding in mouse liver cytosol). 2-Carboxymethylendothal anhydride () was prepared in two steps and 97% overall yield from cis-aconitic anhydride and furan. The potency of was retained on conversion to two 2-carboxymethyl esters but not to two 2-(n-alkylcarboxamidomethyl) analogues.