• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Design of cancer immunostimulant peptide by designable proteomix

Research Project

Project/Area Number 15360439
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionNagoya University

Principal Investigator

HONDA Hiroyuki  Nagoya University, Graduate School of Engineering, Professor, 大学院・工学研究科, 教授 (70209328)

Co-Investigator(Kenkyū-buntansha) KUNIMATSU Mitoshi  Nagoya Women's University, Department of Home Economics, Professor, 家政学部, 教授 (70145746)
ITO Akira  Nagoya University, Graduate School of Engineering, Assistant Professor, 大学院・工学研究科, 助手 (60345915)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsPeotide / Proteomix / Cancer / Conputational science / Peptide chip / Exhaustive / Immunostimulant / HLA / バイオインフォマティクス / HSP70 / Fas ligand / Angiotensin II
Research Abstract

Peptides, which are small biocompatible molecules with simple structure as compared to proteins, have shown various applications functioning as an antimicrobial molecule, inhibitory drug, targeting molecule, growth factor, and nano-material for biocompatible matrixes. Peptide arrays, developed as the SPOT method by R.Frank, have shown great efficiency in high-throughput screening of peptides for biomedical and pharmaceutical researches. In the SPOT method, activated amino acid monomers are spotted on support, such as cellulose membrane, to form a spatially addressed peptide library with the objective peptide length and order. In this study, we demonstrate the efficiency of our screening strategy in which a peptide array was used for direct peptide-cell interaction. In addition, the data obtained were also analyzed by computational science to establish the new method for functional peptide design, "designable proteomics". Consequently, the following results were obtained.
1)Screening of … More newry functional peptides
Peptide arrays covering the Ang II receptor type 1 sequence were prepared, and the peptide (VVIVIY) within the first transmembrane region exhibited the highest affinity to Ang II. The synthesized soluble VVIVIY peptide bad an 84% inhibitory effect on Ang II-induced aorta contration. In addition, we investigated the efficiency of the use of peptide array for direct cell assay, without cleavage of peptides, to design novel tumor growth-inhibitory peptides. From human Fas antigen ligand sequence, we found a novel 5-mer peptide domain (CNNLP) that strongly inhibits the growth of cancer cells by interaction with cell surface.
2)Analysis of peptide chip data by computational science to establish "designable proteomics"
2-1)HMM model construction for peptide screening
Hidden Markov model was constructed for screening of peptide combined with MHC class II molecule. The prediction acuracy of the model constructed was more than 90%.
2-2)Design of cell death inducing peptide
The effect of substitution of one peptide in the sequence of CNNLP was investigated by peptide chip cell assay system. From computational analysis of the data, the following rule was obtained to design the functional peptide ; 3 amino acid residues are important for the function and N-terminal amino acid should be small. Especially, threonin or valine is effective.
2-3)Exploring of lipases with inverted enantioselectivity for a substrate
We explored lipases with inverted enantioselectivity from the wild-type bacterial lipase, which is originally selective for (S)-configuration of the substrate. Computational tool constructed by us predicted a rule indicating that "size at position L167," among 4 positions(L17,F119,L167,and L266) in the substrate binding core region, is the most influential factor. Based on the guidelines obtained, we found two engineered novel variants, namely FIGV(L17F,F119I,L167G,and L266V) and FFGI(L17F,L167G,and L266I).
3)Exploring of cancer vaccine peptide
From the sequence of HSP70,the exploring of candidates of cancer vaccine peptide was investigated. HSP70 was one of the cancer specific proteins and a part of protein sequence is possible to become cancer vaccine peptide. From the assay of peptide chip spotting HSP70 sequence, more than 10 candidate peptide was obtained. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 2003 Other

All Journal Article (9 results) Book (1 results) Patent(Industrial Property Rights) (1 results) Publications (3 results)

  • [Journal Article] Novel Strategy for Protein Exploration : High-Throughput Screening Assisted with Fuzzy Neural Network2005

    • Author(s)
      R.Kato, H.Nakano, H.Konishi, K.Kato, Y.Koga, T.Yamane
    • Journal Title

      Journal of Molecular Biology 3452(印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel Strategy for Protein Exploration : High-Throughput Screening Assisted with Fuzzy Neural Network2005

    • Author(s)
      R.Kato, H.Nakano, H.Konishi, K.Kato, Y.Koga, T.Yamane, T.Kobayashi, H.Honda
    • Journal Title

      Journal of Molecular Biology vol.3452(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiotensin II inhibitory peptide found in the receptor sequence using peptide array2004

    • Author(s)
      Ryuji Kato, Mitoshi Kunimatsu, Takeshi Kobayashi, Hiroyuki Honda
    • Journal Title

      Biochemical and Biophysical Research Communications 315

      Pages: 22-29

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiotensin II inhibitory peptide found in the receptor sequence using peptide array2004

    • Author(s)
      Ryuji Kato, Mitoshi Kunimatsu, Takeshi Kobayashi, Hiroyuki Honda
    • Journal Title

      Biochemical and Biophysical Research Communications vol.315

      Pages: 22-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hidden Markov model-based approach as the first screening of binding peptides that interact with MHC class II molecules2003

    • Author(s)
      Ryuji Kato, Hideki Noguchi, Hiroyuki Honda, Takeshi Kobayashi
    • Journal Title

      Enzyme and Microbial Technology 33

      Pages: 472-481

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hidden Markov model-based approach as the first screening of binding peptides that interact with MHC class II molecules2003

    • Author(s)
      Ryuji Kato, Hideki Noguchi, Hiroyuki Honda, Takeshi Kobayashi
    • Journal Title

      Enzyme and Microbial Technology vol.33

      Pages: 472-481

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Informatics supporting the research field of nanotechnology(in Japanese)2003

    • Author(s)
      H.Honda, R.Kato
    • Journal Title

      Front Line of Nanobiotechnology(ed., M.Ueda)(CMC Shuppan)

      Pages: 439-439

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Direct cell assay on peptide array is effective for functional peptide design

    • Author(s)
      R.Kato, Y.Okuno, C.Kaga, M.Kunimatsu, T.Kobayashi, H.Honda
    • Journal Title

      Biochemical and Biophysical Research Communications (submitted)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Novel Strategy for Protein Exploration : High-Throughput Screening Assisted with Fuzzy Neural Network

    • Author(s)
      R.Kato, H.Nakano, T.Yamane, T.Kobayashi, H.Honda 他3名
    • Journal Title

      Journal of Molecular Biology (submitted)

    • Related Report
      2004 Annual Research Report
  • [Book] ナノ バイオテクノロジーの最前線2003

    • Author(s)
      本多裕之, 加藤竜司
    • Total Pages
      439
    • Publisher
      シーエムシー出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 細胞死誘導のためのペプチドおよび医薬2003

    • Inventor(s)
      小林 猛, 加藤 竜司, 本多 裕之, 奥野 郁佳子, 国松 己歳
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Number
      2009-287727
    • Filing Date
      2003-08-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ryuji Kato, Mitoshi Kunimatsu, Takeshi Kobayashi, Hiroyuki Honda: "Angiotensin II inhibitory peptide found in the receptor sequence using peptide array"Biochemical and Biophysical Research Communications. 315. 22-29 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ryuji Kato, Hideki Noguchi.Hiroyuki Honda, Takeshi Kobayashi: "Hidden Markov model-based approach as the first screening of binding peptides that interact with MHC class II molecules"Enzyme and Microbial Technology. 33. 472-481 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 本多裕之, 加藤竜司: "ナノ バイオテクノロジーの最前線"シーエムシー出版. 439 (2003)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi