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Design and Improvement of Food Proteins by the Introduction of New Function

通过引入新功能来设计和改进食品蛋白质

基本信息

批准号：
03660134
负责人：
YOSHIKAWA Masaaki
金额：
$ 1.34万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03660134/
关键词：
food protein casein peptide casoxin bradykinin endothelium opioid gluten

项目摘要

Biologically active peptides are screened for in enzymatic digests of food proteins. Derivatives of theses peptides were synthesized and their structure-activity relationships were studied to design orally effective biologically active peptides, which could be introduced into food proteins by protein engineering. Casoxin C, Tyr- Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg, which is released from bovine kappa-casein by the action of trypsin is a multifunctional peptide. Homology is found between the penta- peptide sequence at the carboxyl terminus of casoxin C and the laminin penta-peptide, Tyr-Ile-Gly-Ser-Arg. Unlike laminin penta-peptide, casoxin C or pepta-peptide at its carboxyl terminus did not inhibit tumor metastasis. The [Ile^7,Gly^8]-casoxin C, which has laminin penta-peptide sequence at the carboxyl terminus inhibited tumor metastasis in mice.Casoxin D, Tyr-Val-Pro-Phe-Pro-Pro-Phe, is a vaso-relaxing peptide derived from human alpha_<51>-casein. Casoxin D binds to bradykinin BK1-receptors of endothelium. The endothelium-derived relaxing factor released by casoxin D stimulusis is prostacyclin. Among casoxin D derivatives synthesized, Tyr-Pro-Phe-Pro-Pro-Phe, Val-Val-Phe-Pro- Pro-Phe and Tyr-Val-Phe-Pro-Pro-Phe showed vaso-relaxing activity at the concentrations 1/4, 1/7 and 1/10 that of casoxin D. Tyr-Pro-Phe-Pro-Pro-Phe lowered blood pressure of spontaneously hypertensive rats after oral administration while other peptides were active only after intravenous administration. Another derivative Tyr- Pro-Phe-Pro-Pro-Leu showed vaso-relaxing activity at the concentration 1/10,000 that of casoxin D. Mode of action of this peptide was different from that of casoxin D.Opioid peptides were isolated from enzymatic digests of wheat gluten and potent derivatives were obtained by substitution of single amino acid residues.

在食品蛋白质的酶消化物中筛选生物活性肽。合成了这些肽的衍生物，并研究了它们的构效关系，以设计口服有效的生物活性肽，可以通过蛋白质工程将其引入食品蛋白质中。 Casoxin C，Tyr-Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg，通过胰蛋白酶的作用从牛 kappa-酪蛋白中释放出来，是一种多功能肽。在酪蛋白 C 羧基末端的五肽序列和层粘连蛋白五肽 Tyr-Ile-Gly-Ser-Arg 之间发现同源性。与层粘连蛋白五肽不同，羧基末端的酪蛋白C或肽不抑制肿瘤转移。 [Ile^7,Gly^8]-casoxin C，在羧基末端具有层粘连蛋白五肽序列，可抑制小鼠肿瘤转移。Casoxin D，Tyr-Val-Pro-Phe-Pro-Pro-Phe，是一种源自人 α_51>-酪蛋白的血管舒张肽。 Casoxin D 与内皮细胞的缓激肽 BK1 受体结合。酪蛋白 D 刺激物释放的内皮源性舒张因子是前列环素。合成的酪蛋白 D 衍生物中，Tyr-Pro-Phe-Pro-Pro-Phe、Val-Val-Phe-Pro-Pro-Phe 和 Tyr-Val-Phe-Pro-Pro-Phe 在浓度为酪蛋白 D 的 1/4、1/7 和 1/10 时表现出血管舒张活性。Tyr-Pro-Phe-Pro-Pro-Phe 口服后可降低自发性高血压大鼠的血压同时其他肽仅在静脉内给药后才具有活性。另一种衍生物 Tyr-Pro-Phe-Pro-Pro-Leu 在浓度为 casoxin D 的 1/10,000 时显示出血管舒张活性。该肽的作用方式与 casoxin D 不同。阿片肽是从小麦麸质的酶消化物中分离出来的，并通过单个氨基酸残基的取代获得了有效的衍生物。