Soymorphins, Novel μ Opioid Peptides Derived from Soy β-Conglycinin β-Subunit, Have Anxiolytic Activities

Based on the amino acid sequence YPFV found in the soy β-conglycinin β-subunit, which is common to an opioid peptide human β-casomorphin-4, peptides YPFVV, YPFVVN, and YPFVVNA were synthesized according to their primary structure. On guinea pig ileum (GPI) assay, they showed opioid activity (IC50 = 6.0, 9.2 and 13 μM respectively) more potent than human β-casomorphins, and were named soymorphins-5, -6, and -7, respectively. Their opioid activities on mouse vas deferens (MVD) assay were less potent than on GPI assay, suggesting that they are selective for the μ opioid receptor. Human β-casomorphin-4 and soymorphin-5 were released from the soy 7S fraction (β-conglycinin) by the action of gastrointestinal proteases. Soymorphins-5, -6, and -7 had anxiolytic activities after oral administration at doses of 10–30 mg/kg in the elevated plus-maze test in mice.

[1]  M. Sugano,et al.  Bioactive peptides derived from soy protein. , 2006 .

[2]  A. Lipkowski,et al.  Rubiscolin, a delta selective opioid peptide derived from plant Rubisco. , 2001, FEBS letters.

[3]  J. Slightom,et al.  Isolation and characterization of a genomic clone encoding the β-subunit of β-conglycinin , 1987, Planta.

[4]  M. Kasuga,et al.  Endomorphins have orexigenic and anxiolytic activities in mice , 1998, Neuroreport.

[5]  Liping Chen,et al.  Structure–activity relationship of rubiscolins as δ opioid peptides , 2003, Peptides.

[6]  F. Lottspeich,et al.  Novel opioid peptides derived from casein (beta-casomorphins). I. Isolation from bovine casein peptone. , 1979, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[7]  M Tanaka,et al.  Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. , 2000, European journal of pharmacology.

[8]  H. Chiba,et al.  Opioid Peptides from Human β-Casein , 1984 .

[9]  N. Maruyama,et al.  Soybean β-Conglycinin Diet Suppresses Serum Triglyceride Levels in Normal and Genetically Obese Mice by Induction of β-Oxidation, Downregulation of Fatty Acid Synthase, and Inhibition of Triglyceride Absorption , 2004, Bioscience, biotechnology, and biochemistry.

[10]  Masaaki Yoshikawa,et al.  Rubiscolin-6, a δ opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating σ1 and dopamine D1 receptors , 2007, Peptides.

[11]  M. Yoshikawa,et al.  Gluten exorphin C , 1993, FEBS letters.

[12]  A. Kastin,et al.  A potent and selective endogenous agonist for the µ-opiate receptor , 1997, Nature.

[13]  F. Lottspeich,et al.  Novel opioid peptides derived from mitochondrial cytochrome b: cytochrophins. , 1985, European journal of pharmacology.

[14]  S. Snyder,et al.  Historical review: Opioid receptors. , 2003, Trends in pharmacological sciences.

[15]  A. Lipkowski,et al.  Rubiscolin, a δ selective opioid peptide derived from plant Rubisco , 2001 .

[16]  M. Yoshikawa,et al.  Opioid peptides derived from wheat gluten: Their isolation and characterization , 1992, FEBS letters.