An exhaustive search of new bioactive peptides based on prediction by bioinformatics using human genome structures

基于使用人类基因组结构的生物信息学预测对新生物活性肽进行详尽的搜索

• 批准号: 17590214
• 负责人: KIMURA Sadao
• 金额: $ 2.37万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590214/
• 关键词: GPCR; orphan GPCR; bioactive peptide; genome structure; bioinformatics; バイオインフォーマティクス

1) Based on biosynthetic rules of known peptide hormones, we tried to predict candidate bioactive peptides from human genome structure as peptide ligands for orphan G protein-coupled receptors (GPCRs).2) We developed a program to predict bioactive peptide ligands and predicted 1750 candidate peptides for GPCRs and synthesized them by chemical synthesis.3) To find out new ligands for orphan GPCRs, we measured bioactivity of these synthetic peptides using 26 kinds of cells for detecting changes in their intracellular calcium concentration induced by these peptides.4) We detected 140 peptides, which had activity. However, it was found that all these peptides are active on cells only in a range of high concentrations (more than 10^<-6> M).5) It seemed that candidate peptides crossed-acted on orphan GPCRs and produced a intracellular calcium signal, and it was estimated that these were not true GPCR ligands because known bioactive peptides are active in a concentration range of 10^<-9> -10^<-8> M.6) Further improvement of program software to predict candidate peptides from genome structures is needed, and it seems that development of new screening methods to detect bioactive peptides effectively, in addition to the intracellular calcium assay, is essential.

1)根据已知肽类激素的生物合成规律，我们尝试从人类基因组结构中预测作为孤儿G蛋白偶联受体（GPCRs）配体的候选生物活性肽。2）我们开发了一个预测生物活性肽配体的程序，预测了1750个GPCRs的候选肽，并通过化学合成的方法合成了它们。我们用26种细胞检测这些合成肽的生物活性，以检测这些肽诱导的细胞内钙浓度的变化。4）我们检测了140个具有活性的肽。然而，发现所有这些肽仅在高浓度范围内（超过10 μ M）对细胞有活性<-6>。5）候选肽似乎与孤儿GPCR交叉作用并产生细胞内钙信号，并且估计这些不是真正的GPCR配体，因为已知的生物活性肽在10 μ M-10 μ M的浓度范围内有活性<-9>。6）需要进一步改进程序软件以从基因组结构预测候选肽<-8>，并且似乎除了细胞内钙测定之外，开发新的筛选方法来有效地检测生物活性肽是必要的。

项目成果

Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of tumor cells.

p38α 丝裂原激活蛋白激酶参与肿瘤细胞的肺转移。

• 发表时间: 2006
• 期刊: J. Biol. Chem. 281
• 作者: Matsuo Y;Amano S;Furuya M;Namiki K;Sakurai K;Nishiyama M;Sudo T;Tatsumi K;Kuriyama T;Kimura S;Kasuya Y.
• 通讯作者: Kasuya Y.

Involvement of p38alpha mitgen-activayed protein kinase in lung metastasis of tumor cells.

p38α 丝裂原激活蛋白激酶参与肿瘤细胞的肺转移。

• 发表时间: 2006
• 期刊: J. Biol. Chem. 281・48
• 作者: Matsuo Y;Amano S;Furuya M;Namiki K;Sakurai K;Nishiyama M;Sudo T;Tatsumi K;Kuriyama T;Kimura S;Kasuya Y
• 通讯作者: Kasuya Y

Pathophysiology of tumor neovascularization.

• DOI: 10.2147/vhrm.2005.1.4.277
• 发表时间: 2005
• 期刊: Vascular health and risk management
• 影响因子: 2.9
• 作者: Furuya M;Nishiyama M;Kasuya Y;Kimura S;Ishikura H
• 通讯作者: Ishikura H