Pepstatin Inhibition Mechanism

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Pepstatin is a strong inhibitor for all acid proteases. It does not inhibit other groups of proteases, such as the neutral and alkaline proteases (1). The unusual potency of pepstatin toward acid proteases is indicated by its Ki which was reported by Kunimoto et al. (2) to be about 1 × 10−10 M for porcine pepsin. Although its chemical structure has been shown (3) to be a hexapeptide which contains two residues of an unusual amino acid, 4-amino-3-hydroxy-6-methylhepatanoic acid (statine), the mode of inhibition by pepstatin is unknown.