Cleavage of oligopeptide p-nitroanilides attached to N-(2-hydroxypropyl)methacrylamide copolymers by guinea pig intestinal enzymes
Cleavage of oligopeptide p-nitroanilides attached to N-(2-hydroxypropyl)methacrylamide copolymers by guinea pig intestinal enzymes
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豚鼠肠道酶裂解 N-(2-羟丙基)甲基丙烯酰胺共聚物上附着的寡肽对硝基苯胺
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
J. Kopeček
中科院分区：
文献类型：
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作者：
P. Kopečková;K. Ikesue;J. Kopeček
合成了以对硝基苯胺为端基的寡肽N-（2-羟丙基）甲基丙烯酰胺共聚物和低分子量寡肽对硝基苯胺。它们被用作底物，以评估在豚鼠胃肠道中的酶活性。从豚鼠小肠和结肠中分离刷状缘膜酶和管腔酶（上清液和沉淀），并在体外研究底物的切割。结果表明小肠和结肠刷状缘中存在内肽酶活性。Phosphoramidon是一种有效的内肽酶-24.11抑制剂，它对低分子量底物的切割有效，但对聚合物底物的切割无效，这表明不同的内肽酶参与了后者的切割。管腔酶更活跃的裂解聚合物底物（相比于低分子量的），根据胃肠道的生理功能。肠腔和刷状缘的酶活性在结肠中显著低于小肠。这表明结肠可能是口服递送肽和蛋白质的合适位点。
N-(2-Hydroxypropyl)methacrylamide copolymers containing oligopeptide side chains terminated with p-nitroaniline, and low-molecular-weight oligopeptide p-nitroanilides, were synthesized. They were used as substrates to evaluate the enzymatic activity in the gastrointestinal tract of guinea pigs. Brush border membrane enzymes and luminal enzymes (supernatant and pellet) were isolated from guinea pig small intestine and colon, and the cleavage of the substrates was studied in vitro. The results indicate the presence of endopeptidase activity in both small intestine and colon brush border. Phosphoramidon, a potent inhibitor of endopeptidase-24.11, was effective in the cleavage of low-molecular-weight substrates, but ineffective in the cleavage of polymeric substrates, indicating the participation of a different endopeptidase in the cleavage of the latter. Luminal enzymes were more active in the cleavage of polymeric substrates (when compared to low-molecular-weight ones) in accordance with the physiological function of the gastrointestinal tract. The enzymatic activity, both luminal and brush border, was considerably lower in the colon than in the small intestine. This suggests that the colon might be a suitable site for the oral delivery of peptides and proteins.