Harish Kumar P M, Kassell B
Biochemistry. 1977 Aug 23;16(17):3846-9. doi: 10.1021/bi00636a020.
The peptide Leu-Val-Lys-Val-Pro-Leu-Val-Arg-Lys-Lys-Ser-Leu-Arg-Gln-Asn-Leu, a known pepsin inhibitor, is derived from the first 16 amino acids of porcine pepsinogen. It was prepared from the activation mixture and was modified by guanidination of its three lysine residues to form homoarginine residues. The modified peptide is a better pepsin inhibitor than the native peptide; for 50% inhibition of the milk clotting action of pepsin at pH 5.3, the molar ratio of peptide to pepsin required is 9 for the native inhibitor and only 2 for the guanidinated inhibitor. The dissociation constants (k1) of the inhibitor-pepsin complexes are 7 X 10(-8) and 1.4 X 10(-8) M for the native and guanidinated peptides, respectively. The guanidinated peptide is more resistant to digestion by pepsin at pH 3.5. The native and modified peptides partially protect pepsin from inactivation at pH 7. Stepwise removal of the amino-terminal Leu-Val-Har residues from the guanidinated inhibitor by Edman degradation decreases the pepsin-inhibiting activity only slightly at the first step, but markedly at the second and third steps. Thus, all of the amino-terminal sequence except the leucine residue is necessary for full activity.
肽Leu-Val-Lys-Val-Pro-Leu-Val-Arg-Lys-Lys-Ser-Leu-Arg-Gln-Asn-Leu是一种已知的胃蛋白酶抑制剂，它源自猪胃蛋白酶原的前16个氨基酸。它是从活化混合物中制备的，并通过对其三个赖氨酸残基进行胍基化修饰形成高精氨酸残基。修饰后的肽比天然肽是更好的胃蛋白酶抑制剂；在pH 5.3条件下，对于胃蛋白酶凝乳作用50%的抑制，天然抑制剂所需的肽与胃蛋白酶的摩尔比为9，而胍基化抑制剂仅为2。抑制剂 - 胃蛋白酶复合物的解离常数（k1）对于天然肽和胍基化肽分别为7×10^(-8)和1.4×10^(-8) M。胍基化肽在pH 3.5时对胃蛋白酶的消化更具抗性。天然肽和修饰后的肽在pH 7时可部分保护胃蛋白酶不被失活。通过埃德曼降解从胍基化抑制剂中逐步去除氨基末端的Leu-Val-Har残基，在第一步时仅略微降低胃蛋白酶抑制活性，但在第二步和第三步时显著降低。因此，除亮氨酸残基外的所有氨基末端序列对于完全活性都是必需的。
