Alkylation of brain corticosteroid acetyltransferase by 17-hydroxyprogesterone 17-(9-oxo-10-chlorodecanoate) and related compounds

The addition of 17-hydroxyprogesterone 17-(9-oxo-10-chlorodecanoate) (1) at 1.5 μM to a partially purified preparation of corticosteroid acetyl-transferase from the primate brain at pH 7.4, results in a 50% inhibition of enzymatic activity after 30 minutes at 37°. At this concentration the analogous 9-oxo-10-diazodecanoate, 8-carbomethyoxyoctanoate or 8-carboxyoctanoate esters show no effect on the activity of this enzyme. 9-Oxo-10-chlorodecanoate and its methyl ester are respectively 0.44 and 0.07-fold as effective inhibitors as 1. The inhibition by 1 has been shown to be non-competitive and irreversible. There is no reaction of 1 with amino acids, glutathione, or human or bovine serum mercaptalbumin in a pH 7.4 phosphate buffer at 37°, demonstrating the partial specificity of this alkylating agent.