CYCLOPROPYLAMINES AS SUICIDE SUBSTRATES FOR CYTOCHROMES-P-450

There is considerable current interest in enzyme inhibitors of the fecat or suicide substrate variety.1 Because the action of such inhibitors is intimately related to the enzymatic mechanism, knowledge of the latter often provides an excellent starting point for the rational design of highly specific and effective inhibitors. Conversely, the discovery of such inhibitors for an enzyme whose mechanism and active site are not well characterized should, in principle, provde an equally specific and effective probe of catalytic mechanism and activesite structure for that enzyme. The cytochrome P-450 mixed-function oxidases constitute an important family of enzymes whose mechanism and active sites remain incompletely characterized despite more than a decade of intense effort. A recent report2 that allylisopropylacetamide (AIA), long known for its ability to deplete cytochrome P-450 in vivo, undergoes metabolic activation in vivo, leading to its covalent attachment to the heme group of P-450, now prompts us to report our own work with cyclopropylamines as suicide substrates for cytochrome P-450. © 1979, American Chemical Society. All rights reserved.