Opioid antagonist peptides derived from kappa-casein.

Opioid antagonists were sought in the fragments of kappa-casein which were obtained by chemical synthesis and enzymic digestion. A synthetic bovine kappa-casein peptide (35-41), Tyr-Pro-Ser-Tyr-Gly-Leu-Asn (casoxin A) showed opioid antagonist activity at 200 microM in the guinea pig ileum assay. A synthetic peptide Tyr-Pro-Tyr-Tyr (casoxin B) which is found in bovine and human kappa-casein, also showed opioid antagonist activity at 100 microM. Another opioid antagonist peptide (casoxin C) was isolated from tryptic digests of bovine kappa-casein by reverse-phase HPLC. The structure of the peptide was Tyr-Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg, which corresponded to kappa-casein (25-34). Casoxin C was active at 5 microM in the guinea pig ileum assay. Thus, bovine kappa-casein contains three potential opioid antagonist sequences.