Grant-in-Aid for Scientific Research (C)
|Research Institution||Suntory lnstitute for Bioorganic Research (SUNBOR)|
MINAKATA Hiroyuki SUNBOR,Chief Chemist, 主任研究員 (90150143)
NOMOTO Kyosuke SUNBOR,Chief Chemist, 部長研究員 (60142080)
IKEDA Tetsuya Miyazaki Medical College, Division of Biology, Lecturer, 医学部, 講師 (20264369)
YASUDA Yoshimi SUNBOR,Researcher, 研究員 (10270571)
IWASHITA Takashi SUNBOR,Chief Chemist, 主任研究員 (00150144)
SATAKE Honoo SUNBOR,Researcher, 研究員 (20280688)
|Project Fiscal Year
1994 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥900,000 (Direct Cost : ¥900,000)
|Keywords||D-Amino acid / Bioactive peptides / Molluscs / D-アミノ酸 / 生理活性ペプチド / 軟体動物 / 無脊椎動物 / 立体構造|
1.Screening of novel bioactive peptides from invertebrates
(1) RGW amide was isolated from the ventral nerve cord of the echiuroid worm, Urechis unicinctus. The peptide was suggested to inhibit the release of serotonin, the excitatory neurotransmitter or modulator.
(2) A novel D-amino acid-containing peptide, Helix CCAP-RP was isolated from the ganglia of the snail, Helix pomatia. The peptide contained D-Phe residue at position 2 like other D-amino acid-containing peptides isolated so far. L-isomer was also isolated from the ganglia. L-isomer showed varios activity on bioassay using molluscan muscle tissues, whereas did not D-isomer.
2. Structure-activity relationship of D-amino acid-containing peptide, fulicin
The role of D-Asn residue of fulicin was suggested to be the stabilization of specific stereostructure favorable for interaction with receptors.
3. The structure of precursor protein of fulicin
The cDNA encoding a precrsor protein of fulicin was cloned from the ganglia of the African giant snail. The D-Asn residue was encoded by a normal codon corresponding to Asn. Fulicin was franked by -K-R-at the N-terminus and by-G-K-R-at the C-terminus, resulting in the mature peptide by processing and C-termins amidation, and by unknown D-/L-amino acid isomerization.
4. Roles of D-amino acid residue
Three possible roles of D-amino acid residue have been discussed as follows : stabilization of specific stereostructure suitable for binding to receptors : modulation of the biological activity, thereby generating biological diversity : increasing the resistance to exzymatic degradation and expanding biological half-life of peptides. In the case of Helix CCAP-RP,inactivation might be involved in the possible roles.
5. Activity of invertebrate peptides against vertebrate tissues
Analog peptides of fulicin revealed opioid peptide-like activity, and bound to opioid receptors in rat brain.