Abstract
The inhibitory behavior of simple N-protected amino acids containing a difunctional enol group was analyzed. Pseudo-Hill coefficients below 0.5 were obtained for the enol compounds. The active moiety of the enols described herein is involved in an equilibrium between keto and enol forms. The enol in its E form interacts strongly with the enzyme and we suggest that the Z form is expelled from the active site, as suggested by molecular modeling studies using the docking technique. Also, tetrahedral intermediate mimicry is achieved by the enol form, but not by the corresponding keto form. A pseudo-Hill coefficient of 0.25 has been determined for the Boc-phenylalanine enol, and by multiplying the concentration of inhibitor by its pseudo-Hill coefficient, a Ki of 0.82 μM has been determined for the inhibitory E-enol form. Boc-tyrosine enol generated a Ki of 0.39 μM. The requirements at the P1′ position to achieve good inhibition are also described.
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