Specific Enzyme Inactivators in Vitro and in Vivo

Abstract

Highly specific enzyme inactivators can be designed by incorporating latent reactive groupings into substrate analogs of the target enzyme. Upon enzymatic turnover, the reactive group is unmasked. This can result in the specific inactivation of the enzyme if the enzyme reacts with an active-site moiety without diffusing out of the active-site region. Inactivators of this type have been called mechanism-based, suicide, or k _cat inactivators [1]. The purpose of this article is not to write a comprehensive review on these inactivators but rather to illustrate elements of their design and in vivo activities by focusing just on inactivators of γ-aminobutyric acid (GABA) metabolism.