Synthesis and Characterization of a Slow-Binding Inhibitor of Biotin Carboxylase

摘要

Biotin carboxylase catalyzes the ATP-dependent caiboxylation of biotin via a caiboxyphosphate intermediate. It is one component of Escherichia coli acetyl Co A carboxylase which catalyzes the first committed step in the biosynthesis of long-chain fatty-acids. An inhibitor of biotin carboxylase where biotin with phosphonoacetic acid attached to the 1' N is described. The biotin-derived inhibitor was synthesized with a mild, highly selective acylation method. The inhibitor exhibits slow-binding inhibition with a Ki of 0.25 mM which is 400-fold less than the Km for biotin (100 mM). The biotin-phosphonoacetate analog represents the first biotin-derived inhibitor of biotin carboxylase and should prove useful in crystallographic studies.