Guggi A, Tomatis R, Periotto V, Rocchi R
Int J Pept Protein Res. 1976;8(1):79-85.
Synthesis is described of the protected tetrapeptide corresponding to positions 11-14 of the primary structure of the porcine pancreatic secretory trypsin inhibitor II (Kazal), in the form of free acid as well as protected hydrazide. The tetrapeptide tert-butyloxycarbonylglycyl-S-acetamidomethylcysteinylprolyl-Nepsilon-trifluoroacetyl-lysine was prepared by stepwise elongation from the C-terminal Nepsilon-trifluoroacetyllysine using successively 1-succinimidyl benzyloxycarbonylprolinate, p-nitrophenyl N-tert-butyloxycarbonyl-S-acetamidomethylcysteinate and 1-phenyl-3-methyl-4-(tert-butyloxycarbonylglycyl)-oximinyl-5-(benzyloxycarbonylglycyl)-imino-2-pyrazoline as acylating agents. Alternately, the dipeptide benzyloxycarbonylprolyl-Nepsilon-trifluoroacetyllsine was transformed into the corresponding tert-butyloxycarbonylhydrazide which was reacted, after catalytic hydrogenolysis, with tritylglycyl-S-acetamido-methylcysteine to give the tetrapeptide tritylglycyl-S-acetamidomethylcysteinylprolyl-Nepsilon-trifluoroacetyllsine tert-butyloxycarbonylhydrazide. The stereochemical homogeneity of the final products was assessed, after partial deprotection with aqueous 90% trifluoroacetic acid, by digestion with papain and aminopeptidase M, followed by quantitative amino acid analysis.
描述了猪胰分泌性胰蛋白酶抑制剂II（卡扎尔）一级结构中第11 - 14位对应的保护四肽的合成，其形式为游离酸以及保护酰肼。通过从C端的Nε-三氟乙酰赖氨酸逐步延长来制备四肽叔丁氧羰基甘氨酰-S-乙酰氨基甲基半胱氨酰脯氨酰-Nε-三氟乙酰赖氨酸，依次使用1-琥珀酰亚胺基苄氧羰基脯氨酸酯、对硝基苯基N-叔丁氧羰基-S-乙酰氨基甲基半胱氨酸酯和1-苯基-3-甲基-4-(叔丁氧羰基甘氨酰)-肟基-5-(苄氧羰基甘氨酰)-亚氨基-2-吡唑啉作为酰化剂。另外，将二肽苄氧羰基脯氨酰-Nε-三氟乙酰赖氨酸转化为相应的叔丁氧羰基酰肼，在催化氢解后，使其与三苯甲基甘氨酰-S-乙酰氨基甲基半胱氨酸反应，得到四肽三苯甲基甘氨酰-S-乙酰氨基甲基半胱氨酰脯氨酰-Nε-三氟乙酰赖氨酸叔丁氧羰基酰肼。在用90%的三氟乙酸水溶液进行部分脱保护后，通过用木瓜蛋白酶和氨肽酶M消化，然后进行定量氨基酸分析，来评估最终产物的立体化学纯度。
