Marciniszyn J, Hartsuck J A, Tang J
J Biol Chem. 1976 Nov 25;251(22):7088-94.
Four derivatives of pepstatin, each of which contains the unusual amino acid 4-amino-3-hydroxy-6-methylheptanoic acid (statine) have been prepared. All four are porcine pepsin inhibitors. Both N-acetylstatine and N-acetyl-alanyl-statine are competitive inhibitors for pepsin with Ki values of 1.2 X 10(-4) M and 5.65 X 10(-6) M, respectively. The Ki values for N-acetyl-valyl-statine is 4.8 X 10(-6) M. These statyl derivatives, therefore, are very strong inhibitors. The Ki value for N-acetyl-statine is 600-fold smaller than that of its structural analog N-acetyl-leucine. The derivative which contains two statyl residues in a tetrapeptide exhibits inhibitory properties which approach those of pepstatin itself. Other acid proteases, human pepsin, human gastricsin, renin, cathepsin D, the acid protease from Rhizopus chinensis and bovine chymosin, also are inhibited by pepstatin and its derivatives. It is suggested that the statyl residue is responsible for the unusual inhibitory capability of pepstatin and that statine is an analog of the previously proposed transition state for catalysis by pepsin and other acid proteases.
已制备出胃蛋白酶抑制剂的四种衍生物，每种衍生物均含有不寻常的氨基酸4-氨基-3-羟基-6-甲基庚酸（statine）。这四种都是猪胃蛋白酶抑制剂。N-乙酰基statine和N-乙酰基-丙氨酰-statine都是胃蛋白酶的竞争性抑制剂，其Ki值分别为1.2×10⁻⁴M和5.65×10⁻⁶M。N-乙酰基-缬氨酰-statine的Ki值为4.8×10⁻⁶M。因此，这些statyl衍生物是非常强的抑制剂。N-乙酰基statine的Ki值比其结构类似物N-乙酰基亮氨酸的Ki值小600倍。在四肽中含有两个statyl残基的衍生物表现出接近胃蛋白酶抑制剂本身的抑制特性。其他酸性蛋白酶，如人胃蛋白酶、人胃泌素、肾素、组织蛋白酶D、华根霉酸性蛋白酶和牛凝乳酶，也受到胃蛋白酶抑制剂及其衍生物的抑制。有人提出，statyl残基是胃蛋白酶抑制剂具有异常抑制能力的原因，并且statine是先前提出的胃蛋白酶和其他酸性蛋白酶催化过渡态的类似物。
