Rubiscolin, a delta selective opioid peptide derived from plant Rubisco.
We found that the sequences YPLDL and YPLDLF in the large subunit of spinach D-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) met the structure YP-aliphatic amino acid which might have opioid activity. We then synthesized these peptides to test their opioid activity. The IC(50) of these peptides in mouse vas deferens assay were 51.0 microM and 24.4 microM, respectively, and those in delta receptor binding assay using [(3)H]deltorphin II as radioligand were 2.09 microM and 0.93 microM, respectively. Both peptides were selective for delta receptor. We named them rubiscolin-5 and -6, respectively. Rubiscolin-5 and -6 have antinociceptive activity in mice after i.c.v. or oral administration. The enzymatic conditions to release rubiscolin were investigated using both spinach Rubisco and synthetic fragment peptides. This is the first example of bioactive peptides derived from plant Rubisco.
Yang
S
S
Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Yunden
J
J
Sonoda
S
S
Doyama
N
N
Lipkowski
A W
AW
Kawamura
Y
Y
Yoshikawa
M
M
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D004044:Dietary Proteins; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012273:Ribulose-Bisphosphate Carboxylase / Q000737:chemistry* / Q000494:pharmacology*
D000700:Analgesics; D004044:Dietary Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010940:Plant Proteins; D017465:Receptors, Opioid, delta; C443992:rubiscolin 5; C443993:rubiscolin 6; D012273:Ribulose-Bisphosphate Carboxylase