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

• Project/Area Number: 17590214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Chiba University
• Principal Investigator: KIMURA Sadao Chiba University, Graduate School of Medicine, 大学院医学研究院, 教授 (40134225)
• Co-Investigator(Kenkyū-buntansha): KASUYA Yoshitoshi Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助教授 (70221877) ; NISHIYAMA Mariko Chiba University, Graduate School of Medicine, Research Associate, 大学院医学研究院, 助手 (00092081) ; MOROI Kayoko Chiba University, Graduate School of Medicine, Research Associate, 大学院医学研究院, 助手 (80110352)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: GPCR / orphan GPCR / bioactive peptide / genome structure / bioinformatics / バイオインフォーマティクス

Research Abstract

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.

Research Products

• [Journal Article] Involvement of p38alpha mitgen-activayed protein kinase in lung metastasis of tumor cells. (2006)
  • Author(s): Matsuo Y, Amano S, Furuya M, Namiki K, Sakurai K, Nishiyama M, Sudo T, Tatsumi K, Kuriyama T, Kimura S, Kasuya Y
  • Journal Title: J. Biol. Chem. 281・48 Pages: 36767-36775
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of tumor cells. (2006)
  • Author(s): Matsuo Y, Amano S, Furuya M, Namiki K, Sakurai K, Nishiyama M, Sudo T, Tatsumi K, Kuriyama T, Kimura S, Kasuya Y.
  • Journal Title: J. Biol. Chem. 281 Pages: 36767-36775
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pathophysiology of Tumor Neovascularization. (2005)
  • Author(s): Furuya M, Nishiyama M, Kasuya Y, Kimura S, Ishikura H
  • Journal Title: Vasc. Health Risk Management 1・4 Pages: 277-290
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. (2005)
  • Author(s): Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, Kwon YT
  • Journal Title: Proc. Natl. Acad. Sci. USA 102・42 Pages: 15030-15035
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pathophysiology of Tumor Neovascularization. (2005)
  • Author(s): Furuya M, Nishiyama M, Kasuya Y, Kimura S, Ishikura H
  • Journal Title: Vasc. Health Risk Management I(4) Pages: 277-290
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. (2005)
  • Author(s): Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, Kwon YT
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 15030-15035
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pathophysiology of Tumor Neovascularization. (2005)
  • Author(s): Furuya M, Nishiyama M, Kasuya Y, Kimura S, Ishikura H
  • Journal Title: Vasc.Health Risk Management 1・4 Pages: 277-290
• [Journal Article] RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. (2005)
  • Author(s): Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, Kwon YT
  • Journal Title: Proc.Natl.Acad.Sci.USA 102・42 Pages: 15030-15035