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

Endothal (1(diacid)) and [H-3]cantharidic acid ([H-3]CA) bind with high aff inity to the catalytic subunit of protein phosphatase 2A (PP2A). PP2A in li ver cytosol was greatly stabilized with 30% glycerol as a preliminary step in the potential use of endothal-type derivatives for affinity chromatograp hy. We report here the first introduction of a functionalizable group into endothal which allows retention of binding site affinity (assayed as [H-3]C A binding in mouse liver cytosol). 2-Carboxymethylendothal anhydride (7) wa s prepared in two steps and 97% overall yield from cis-aconitic anhydride a nd furan. The potency of 7 was retained on conversion to two 2-carboxymethy l esters but not to two 2-(n-alkylcarboxamidomethyl) analogues. (C) 1999 El sevier Science Ltd. AII rights reserved.