| Co-Investigator(Kenkyū-buntansha) |
IKURA Koji Dept. of Food Sci. and Technol., Faculty of Agric. Kyoto University, 農学部, 助手 (00101246)
YOSHIKAWA Masaaki Dept. of Food Sci. and Technol., Faculty of Agric. Kyoto University, 農学部, 助手 (50026572)
SASAKI Ryuzo Dept. of Food Sci. and Technol., Faculty of Agric. Kyoto University, 農学部, 助教授 (60077378)
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| Budget Amount *help |
¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 1987: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1986: ¥19,000,000 (Direct Cost: ¥19,000,000)
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| Research Abstract |
In order to clarify structures and functions of biologically active peptides derived from food proteins, opioid poptides and immunostimulating peptides were chosen as research targets. Opioid antagonist peptides were isolated from peptic digests of bovine <kappa>-casein (Ser-Arg-Tyr-Pro-Ser-Tyr-OCH_3) and human lactoferrin (Tyr-Leu-Gly-Ser-Gly-Tyr-OCH_3, Arg-Tyr-Tyr-Gly-Tyr-OCH_3 and Lys-Tyr-Leu-Gly-Pro-Gln-Tyr-OCH_3). These opioid antagonist peptides can be expressed as a following general formula, Xa-Tyr-Xb-Tyr-Xc, in which 1) Xa are neutral or basic residues, 2) Tyr near the amino terminus can be replaced by Phe or Trp, 3) Tyr near the carboxyl terminus is essential, 4) Xb are 1 to 4 netral residues, 5) as for Xc, OCH_3 is preferable to OH. From these results, we speculate that these opioid antagonists bind retro-wise to receptors by directing the carboxyl terminal Tyr to binding site for the amino terminal Tyr of opioid agonist peptide.
Based on the primary structures of human and bovine <Kappa>-caseins,Asn-Ser-Tyr-Pro-tyr-Tyr and Leu-Pro-Tyr-Pro-Tyr-Tyr were synthesized. These peptides showed opioid antagonist activities without being esterified.
As a model experiment to introduce biologically active peptide sequence by site directed mutagenesis in the future, fragment peptide of bovine <beta>-casein of which Gly^<203> was converted to Tyr was synthesized. Opioid agonist peptides, Tyr-Pro-Phe-Pro-Ile and Tyr-Pro-Phe-Pro-Ile-Ile, and opioid antagonist peptide, Tyr-Pro-Phe-Pro-Ile-Ile-Val, were obtained form this approach.
Peptide sequences homologous to phagocytosis stimulating peptides, Tuftsin (Thr-Lys-Pro-Arg) and Rigin (Gly-Gln-Pro-Arg), Were searched for in the primary structures of food proteins and and the homologous peptides were synthesized. A fragment peptide of soybean glycinin B_<la> subunit, Gln-Arg-Pro-Arg, stimulated phagocytosis of macrophages.
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