| Project/Area Number |
06672242
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | HOKURIKU UNIVERSITY |
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Principal Investigator |
SAKURA Naiki Hokuriku University, ASSPCIATE PROFESSOR, 薬学部, 助教授 (70046291)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Tadashi Hokuriku University PROFESSOR, 薬学部, 教授 (70046259)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Neuromedin U / Structure-activity relationship / Peptide Synthesis / Agonist / Antagonist / Smooth muscle contraction / Active site / Vasoacitive intestinal polypeptide / ニューロメジン U / アナローグ / プソイドペプチド |
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| Research Abstract |
To develope a neuromedin U antagonist, we synthesized more than seventy analogs of dog neuromedin U-8 (p-Glu^1-Phe^2-Leu^3-Phe^4-Arg^5-Pro^6-Arg^7-Asn^8-NH_2) substituting various amino acids one at a time for each amino acid residue. Agonistic and antagonistic activities of the analogs were evaluated on chicken crop smooth muscle preparation. Structure-activity relationships of dog neuromedin U-8 were summarized as follows :
1 Twentythree analogs modified at position 1 had high contractile activity, suggesting the flexible N-terminal structural requirement to increase the affinity to neuromedin U receptor.
2 The assay results of 26 analogs modified at the hydrohobic N-terminal half region of positions 2-4 showed that both Phe residues are important, especially Phe^2, but not Leu^3. Any X^2-analogs had antagonistic activity.
3 Arg residue of position 7 and alpha-amide of C-terminal Asn were found to be of absolute importance for the biological activity. Modification of Arg^5 and Pro^6 lowered the affinity keeping intrinsic activity. No antagonist was found in Y^7-and Z^8-analogs.
4 Vasoactive intestinal polypeptide (VIP), the C-terminal of which is Asn-NH_2, inhibited the contractile activity of neuromedin U.
Further synthetic work to develope an antagonist and study on mechanism of the function of VIP are under way.
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