Cyclohexenyl and Cyclohexylidene Inhibitors of 3-Dehydroquinate Synthase: Active Site Interactions Relevant to Enzyme Mechanism and Inhibitor Design

摘要

Cyclohexenyl and cyclohexylidene inhibitors possessing strategically placed olefinic residues, in general, bind to 3-dehydroquinate synthase more tightly than similarly substituted cyclohexyl inhibitors. All of the newly synthesized inhibitors were prepared from a common DHQ derivative. Cyclohexenyl phosphate 1 is the most potent inhibitor of DHQ synthase thus far identified with an inhibition constant (K_ⅰ=1.2 *10~-10 M), indicating active site binding 1000-fold tighter relative to the corresponding cyclohexyl phosphate 5.