Structures and Functions of Opioid Peptides Derived from Casein.

对酪蛋白和乳清蛋白来源的阿片肽的分离、化学合成和生物活性进行了研究，以阐明牛奶蛋白的可能生理功能。在&lt；α&gt；-乳清蛋白和&lt；β&gt；-乳球蛋白中分别发现了已知阿片肽常见的多肽序列Tyr-X-Phe和Tyr-X-Y-Phe。合成了相应的多肽酰胺类化合物。这两种多肽在豚鼠回肠测定系统中均表现出较弱的阿片激动剂活性。从牛酪蛋白的消化液中分离到一种与大鼠脑阿片受体有亲和力的多肽。其结构为Ser-Arg-Tyr-Pro-Ser-Tyr-&lt；Och_3&gt；，与酪蛋白的第33-38位残基相对应。在提取过程中，末端的羧基发生了酯化。该多肽在豚鼠回肠测定系统中显示出阿片拮抗剂活性。与Ser-Arg-Tyr-Pro-Ser-Pro-Ser-Tyr-lt；Och_3&gt；Och_3&gt；这些多肽分别命名为酪蛋白4、5和6。合成了人酪蛋白酪蛋白4的同源序列Tyr-Pro-Tyr-Tyr，并对其进行了活性评价。含有游离末端羧基的多肽在200微米处有活性，其甲酯在2微米处有活性，比牛肉毒素4的活性高约10倍。当它们联合注射到小鼠脑室时，可拮抗吗啡的镇痛活性。

Studies on the isolation, chemical syntheses and biological activities of opioid peptides derived from casein and whey proteins were performed to clarify possible physiological functions of milk proteins.Peptide sequences, Tyr-X-Phe and Tyr-X-Y-Phe, which are common to known opioid peptides, were found in <alpha> -lactalbumin and <beta> -lactoglobulin, respectively. The corresponding peptide amides were synthesized. Both peptides showed rather weak opioid agonist activity in the guinea pig ileum assay system.A peptide having affinity for rat brain opioid receptors was isolated from a peptic digest of bovine <kappa> -casein. The structure of the peptide was Ser-Arg-Tyr-Pro-Ser-Tyr- <OCH_3> , which corresponded to the 33-38th residues of <kappa> -casein. The terminal carboxyl group has been esterified during the extraction process. The peptide showed an opioid antagonist activity in the guinea pig ileum assay system. Peptides, Tyr-Pro-Ser-Tyr- <OCH_3> and Arg-Tyr-Pro-Ser-Tyr- <OCH_3> , were as active as Ser-Arg-Tyr-Pro-Ser-Tyr- <OCH_3> . These peptides were named casoxin 4, 5 and 6, respectively. The antagonist activity was retained after the reduction of the terminal Tyr- <OCH_3> to tyrosinol while the peptide with free carboxyl terminal tyrosine had only weak activity.A peptide Tyr-Pro-Tyr-Tyr, the homologous sequence of bovine casoxin 4 found in human <kappa> -casein was synthesized and the antagonist activity was evaluated. The peptide with a free terminal carboxyl group was active at 200 <micro> M. The methyl ester of the peptide, Tyr-Pro-Tyr-Tyr- <OCH_3> , was active at 2 <micro> M and is about 10 times more active than the bovine casoxin 4. The peptide antagonized an analgesic activity of morphiceptin when they are co-injected into mouse intracerebroventricularly.