Hydrolytic enzymes, mechanism-based inactivation

Mechanism-based inhibitors are used as haptens which form covalent intermediates with a suitable antibody allowing the selection of active components. With this approach, different catalysts for several reactions were generated. Mechanism-based inactivators of hydrolytic enzymes have afforded antibodies with esterase, -lactamase,galac-tosidase, and aldolase activity. 

Clavulanic acid is also a mechanism-based inhibitor and its mode of action is believed to involve ring opening of the initially formed acyl-enzyme complex (18) to the keto-derivative (19), which may then tautomerise to the hydrolytically more stable -amino-acrylate (20) Scheme 6.4). This transiently inhibited form may hydrolyse to re-release active enzyme or react further with the enzyme to produce irreversibly inhibited forms. It has been shown that approximately 115 molecules of clavulanic acid are destroyed per molecule of enzyme before the j8-lactamase is irreversibly inactivated. Whilst irreversibly inactivated forms are known to exist, the nature of these products is not yet known. Possible structures are (21) and... 

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