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Physiological and biochemical study of invertebrate peptides

无脊椎动物肽的生理生化研究

基本信息

批准号：
06680568
负责人：
MINAKATA Hiroyuki
金额：
$ 1.47万
依托单位：
Suntory lnstitute for Bioorganic Research (SUNBOR)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06680568/
关键词：
D-Amino acid Bioactive peptides Molluscs 無脊椎動物立体構造

项目摘要

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, fulicinThe 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 fulicinThe 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 residueThree 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 tissuesAnalog peptides of fulicin revealed opioid peptide-like activity, and bound to opioid receptors in rat brain.

1.(1) RGW酰胺从棘针虫（Urechis unicinctus）的腹侧神经索中分离得到。该肽被认为可以抑制兴奋性神经递质或调节剂血清素的释放。(2)从蜗牛的神经节中分离到一种新的含d氨基酸肽Helix CCAP-RP。与迄今为止分离的其他含d氨基酸的肽一样，该肽在2位含有d-苯丙氨酸残基。l -异构体也从神经节中分离出来。l -异构体在软体动物肌肉组织中表现出不同的活性，而d -异构体则没有。含d氨基酸的多肽，fulicin的D-Asn残基的作用被认为是稳定了有利于与受体相互作用的特定立体结构。从非洲巨蜗牛的神经节中克隆了一种黄芩苷前体蛋白的cDNA。D-Asn残基由Asn对应的正常密码子编码。Fulicin在n端被- k - r和c端被g - k - r标记，经过加工和c端酰胺化，以及未知的D-/ l -氨基酸异构化，形成成熟肽。d -氨基酸残基的作用本文讨论了d -氨基酸残基的三种可能作用：稳定适合与受体结合的特定立体结构；调节生物活性，从而产生生物多样性；增加对酶解降解的抗性和延长多肽的生物半衰期。在Helix CCAP-RP的情况下，失活可能涉及到可能的作用。无脊椎动物肽对脊椎动物组织的活性研究富立林的类似肽显示出类阿片肽的活性，并与大鼠脑内的阿片受体结合。