Fundamental Role of the Fostriecin Unsaturated Lactone and Implications for Selective Protein Phosphatase Inhibition
Journal of the American Chemical Society2003Vol. 125(51), pp. 15694–15695
Citations Over TimeTop 12% of 2003 papers
Suzanne B. Buck, Christophe Hardouin, Satoshi Ichikawa, D. R. Soenen, Carla‐Maria Gauss, Inkyu Hwang, Mark R. Swingle, Kathy Bonness, Richard E. Honkanen, Dale L. Boger
Abstract
Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.
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