Derivatives of 2-methyl-1,4-naphthoquinone as substrates and inhibitors of the vitamin K dependent carboxylase.

A series of peptides that contain an N-terminal 2-methyl-1,4-naphthoquinone group or analogues of this structure have been prepared as potential substrates or inhibitors of the rat liver microsomal vitamin K dependent carboxylase. The parent compound, gamma-2-(methyl-1,4-naphthoquinonyl-3)butyryl-Glu-Glu-Leu-OMe, is a good substrate for the carboxylase at low concentrations and has a Km of about 50 microM. This is roughly 2 orders of magnitude lower than the Km of most simple peptide substrates that have been synthesized. Replacement of the 2-methyl-1,4-naphthoquinone group with its desmethyl analogue, a naphthyl, or a stearyl group decreased substrate effectiveness. At higher concentrations, the parent compound and its desmethyl analogue were potent inhibitors of the vitamin K dependent carboxylation reaction. The degree of inhibition exhibited by these peptides was dependent on the vitamin KH2 concentration of the incubation.