ORGN 920 |
| The marine toxin okadaic acid is a potent and selective inhibitor of serine-threonine protein phosphatases. Protein phosphatases (PPs) are a group of enzymes that catalyze the removal of phosphates from amino acid residues in proteins. These enzymes, along with kinases, regulate important cellular signaling pathways. With the wealth of x-ray structural information available for the binding of okadaic acid to PPs, we considered the possibility of designing more synthetically accessible analogues of okadaic acid as potent PP inhibitors. The two functional groups of okadaic acid most important for inhibition - the alpha-hydroxy carboxylic acid and the terminal spiroketal - are known to be active, independently, at sub-micromolar concentrations. We desired to include both these moieties to maximize the potency of our compounds. Consequently, we have designed truncated structures containing a spacer group that holds the two functional groups in the appropriate binding orientation. Progress toward the synthesis of these analogues containing various spacer groups is presented. |
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, August 23, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |