2-Carboxymethylendothal analogues as affinity probes for stabilized protein phosphatase 2A.
Endothal (1diacid) 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 (7) was prepared in two steps and 97% overall yield from cis-aconitic anhydride and furan. The potency of 7 was retained on conversion to two 2-carboxymethyl esters but not to two 2-(n-alkylcarboxamidomethyl) analogues.
Laidley
C W
CW
Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
Dauben
W G
WG
Guo
Z R
ZR
Lam
J Y
JY
Casida
J E
JE
D000345:Affinity Labels / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D003998:Dicarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004795:Enzyme Stability; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D054648:Protein Phosphatase 2; D013329:Structure-Activity Relationship; D013696:Temperature
D000345:Affinity Labels; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2