Structure-activity relationship of diapause hormone analogs and creation of the potent agonists

滞育激素类似物的构效关系和强效激动剂的创建

• 批准号: 10660109
• 负责人: IMAI Kunio
• 金额: $ 1.92万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10660109/
• 关键词: diapause hormone; palmitoyl peptide; lipophilic peptide; peptide derivative; silkworm; peptide synthesis; diapause inducing activity; 親油性蛋白質; 新投薬法; 休眠ホルモン; 脂肪酸誘導体; 休眠誘導活性; トリプシン分解

In the past research, it has been clarified that the C-terminal tri-peptide amide (PRL-NH_2) of diapause hormone (DH) is the minimum structure for biological activity.In the present study, the role of the side-chain group of DH for the activity expression was analyzed by preparing the DH analogs and by analyzing the biological activity. The results are : 1) the amide structure is indispensable for the activity, 2) the positively charged side-chain of Arg of PRL-NH_2 is essential, 3) modification of PRL-NH_2 with acyl group enhances the activity, 4) palmitoyl-NH_2 and stearoyl-PRL-NH_2 show the strongest activity among the tested derivatives.While, the lipophilic peptide isolated from the heads of silkmoths enhanced the activity of DH.The fragment analog of the peptide showed interesting effect on enzymic digestion of DH.It protected the hormone from the digestion by interacting not with the enzyme but with the substrate, DH.Another peptide showing the similar synergistic effect on DH action was searched for in the other arthropods, and one protein, Pb CP-12.7, was isolated from the shell of the shrimp, Pandalus borealis, and its unique structure and lipophilic nature were clarified. These results offered the hint to improve the method for dosage of the hormone.

以往的研究表明，滞育激素（DH）的C-末端三肽酰胺（PRL-NH_2）是其生物活性的最小结构，本研究通过制备DH类似物并对其生物活性进行分析，探讨了DH侧链基团在其活性表达中的作用。其结果是：1）酰胺结构是活性所必需的，2）精氨酸侧链带正电荷是活性所必需的，3）酰基修饰能增强活性，4）棕榈酰-NH_2和硬脂酰-PRL-NH_2活性最强，而从蚕蛾头中分离的亲脂性肽能增强DH的活性，其片段类似物对DH的酶解有明显的影响，它通过与DH的相互作用保护激素不被酶解不是与酶而是与底物DH一起作用。在其他节肢动物中寻找了另一种对DH作用具有类似协同作用的肽，并从北极虾（Pandalus borealis）的壳中分离出一种蛋白质Pb CP-12.7，并阐明了其独特的结构和亲脂性。这些结果为改进激素的给药方法提供了参考。

项目成果

K.Suzuki: "Isolation and characterization of a novel lipophilic protein, Pb CP-12.7, from the shell of pink shrimp, Pandalus borealis"Biosci.Biotechnol.Biochem.. (in press).

K.Suzuki：“从粉红虾、北极虾壳中分离和鉴定一种新型亲脂性蛋白 Pb CP-12.7”Biosci.Biotechnol.Biochem..（出版中）。

Y.Sato: "Phe-X-Pro-Arg-Leu-NH_2 peptide producing cells in the central nervous system of the silkworm,Bombyx mori." J.Insect Physiol.44. 333-342 (1998)

Y.Sato：“家蚕中枢神经系统中产生 Phe-X-Pro-Arg-Leu-NH_2 肽的细胞。”

Kunio Imai: "Minimum structure of diapause hormone required for biological activity"Biosci.Biotechnol.Biochem.. 62(10). 1875-1879 (1998)

Kunio Imai：“生物活性所需的滞育激素的最小结构”Biosci.Biotechnol.Biochem.. 62(10)。

Kunihiro.Shiomi: "Structure of the VAP-peptide (BM ACP-6.7) gene in the silkworm,Bombyx mori and a possible regulation of its expression by BmFTZ-F1"Insect Biochem.Mol.Biol.. 30. 119-125 (2000)

Kunihiro.Shiomi：“家蚕 Bombyx mori 中 VAP 肽 (BM ACP-6.7) 基因的结构以及 BmFTZ-F1 对其表达的可能调节”Insect Biochem.Mol.Biol.. 30. 119-125 (

Kunihiro Shiomi: "A hydrophobic peptide(VAP-peptide)of the silkworm,Bombyx mori:a uniquo role for adult activity proposed from gene expression and production at the terminal phaso of metamorphosis" J.Insect Biochem.Mol.Biol.28. 671-676 (1998)

Kunihiro Shiomi：“家蚕的疏水肽（VAP-肽），家蚕：从变态末期的基因表达和生产中提出的对成虫活性的独特作用”J.Insect Biochem.Mol.Biol.28。