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Generation of bioactive peptides which suppress HIV infection

Research Project

Project/Area Number 10044310
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionNagoya City University

Principal Investigator

OKADA Hidechika  Nagoya City Univ. Sch. Med. Prof., 医学部, 教授 (30160683)

Co-Investigator(Kenkyū-buntansha) WILLIAM Campbell  Choju Med. Inst., Res. Fellow, 長寿医学研究所, 主任研究員
OKADA Noriko  Nagoya City Univ. Sch. Med. Assoc. Prof., 医学部, 助教授 (20160682)
カツァツキン ミッシェル  Hopital Broussais, Clinical Immunology, 教授
クライマン ローレンス  McGill AIDS Centre, 教授
ウェインバーグ マーク  McGill AIDS Centre, 所長
ラジョス バラニ  野依福祉村病院, 長寿医学研究所, 主任研究員 (10244542)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsProtein / Amino acid sequence / Antisense peptide / Antisense homology box / HIV-1 / T20 / gp160 / Electromagnetic resonance / Antisense peptide / antisense homology box / 逆転写酵素 / gp120 / gp41 / T22ペプチド / 電磁気共鳴
Research Abstract

Recently we identified a novel motif in proteins that consists of short amphiphilic regions of 6-20 amino acids expressing strong sense-antisense relationships at the protein level. These regions, termed antisense homology boxes (AHB) are separated by approximately 50 amino acid long regions. It is expected that AHBs may be involved in folding, chaperoning and oligomer formation of proteins. AHB-derived peptides have been shown to possess some biological functions with respect to the endothelin receptor and C5a receptor. We detected AHB regions between gp160 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) and T20, which was a peptide inhibitor of gp41-mediated virus entry, using the "ANTIS" computer program and synthesized peptides. Antisense homology box-derived peptide of gp160, termed T20ASP-1L (amino acids 84-97), shoed inhibitory activity to HIV-1IIIB infection of MT-4 cells. T20ASP-1L site, which exists in gp160 C1 region, was highly homologous each strain of HIV-1 at least 70% over. And T20ASP-1L also inhibited HIV-1MN infection of MT-4 cells weakly. The inhibition of HIV-1 infection by T20ASP-1L (amino acids 84-97) of the gp160 subunit suggests that T20ASP-1L site in C1 region of gp160 may influence something of HIV-1 infection to target cells and biologically active inhibitory peptides can be found by searching for antisense motifs in the target protein.
We also analyzed gp160 with the electromagnetic resonance theory developed by Dr. Irena Cosic and found a specific frequency at T20 region of gp41.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Miwa, T.: "Alternative exon usage in the 3'region of a single gene generates glycosylphosphatidyl-inositol-anchored and transmembrane forms of rat decay-accelerating factor"Immunogenetics. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imai, M.: "Inhibition of HIV-1 infection by an intramolecular antisense peptideto T20 in gp160"Microbiol. Immunol.. 44. 205-212 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mizuno, M.: "Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with LPS"J. Immunol.. 162. 5477-5482 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wu, X.: "Complement mediated anti-HIV-1 effectinduced by human IgM mAb against"J. Immunol. 162. 533-539 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Baranyi, L.: "Antisense homology box derived peptidesrepresent a new class of endothelin eceptor ingibitors"peptides. 19. 211-223 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada, H.: "The possible role of sense and antisense peptide interactions in the generation and maintenance of the tertiary structure of a protein"Anticancer Res.. 18. 3927-3930 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miwa, T., Okada, N. and Okada H.: "Alternative exon usage in the 3'region of a single gene generates glycosylphosphatidylinositol-anchored and transmembrane forms of rat decay-accelerating factor."Immunogenetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Imai, M., Okada, N. & Okada H.: "Inhibition of HIV-1 infection by an intramolecular antisense peptide to T20 in gp160."Microbiol. Immunol.. 44. 205-212 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mizuno, M., Nishikawa, K., Okada, N., Matsuo, S., Ito, K. & Okada, H.: "Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with LPS."J. Immunol.. 162. 5477-5482 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wu, X., Okada, N., Momota, H., Irie, R. F. & Okada, H.: "Complement mediated anti-HIV-1 effect induced by human IgM mAb against ganglioside GM2."J. Immunol.. 162. 533-539 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Baranyi, L., Campbell, W., Ohshima, K.,, Fujimoto, S., Boros, M., Kaszaki, J. & Okada, H.: "Antisense homology box derived peptides represent a new class of endothelin receptor inhibitors."Peptides. 19. 211-223 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada, H.: "The possible role of sense and antisense peptide interactions in the generation and maintenance of the tertiary structure of a protein."Anticancer Res.. 18. 3927-3930 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miwa,T.: "Alternative exon usage in the 3' region of a single gene generates glycosylphosphatidyl-inositol-anchored and transmembrane forms of rat decay-accelerating factor"Immunogenetics. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Imai,M.: "Inhibition of HIV-1 infection by an intramolecular antisense peptide to T20 in gp160"Microbiol.Immunol.. 44. 205-212 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mizuno,M.: "Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with LPS"J.Immunol.. 162. 5477-5482 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wu,X.: "Complement mediated anti-HIV-1 effect induced by human IgM mAb against ganglioside GM2"J.Immunol.. 162. 533-539 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Baranyi,L.: "Antisense homology box derived peptides represent a new class of endothelin receptor inhibitors"Peptides. 19. 211-223 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okada,H.: "The possible role of sense and antisense peptide interactions in the generation and maintenance of the tertiary structure of a protein"Anticancer Res.. 18. 3927-3930 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wu,X.: "Complement-mediated anti-HIV1 effect induced by human IgM monoclonal antibody against ganglioside GM2^1" J.Immunol.162. 533-539 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okada,H.: "Complement mediated cytolysis and azidothymidine are synergistic in HIV-1 suppression." Int.Immunol.10. 91-95 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Boros,M.: "Endothelin 1 induces leukpcute adhesion in submucosal venules of the rat small intestine." Gastroenterology. 114. 103-114 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Farkas,I.: "Neuronal C5a receptor and an associated apoptotic signal transduction pathway." J.Physiol.507. 679-687 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Baranyi,L.: "Antisense homology box derived peptides represent a new class of endothelin receptor inhibitors." Peptides. 19. 211-223 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,G.: "Functional differences among multiple isoforms of guinea pig decay accelerating factor (DAF)." J.Immunol.160. 3014-3022 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Farkas E.: "Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells." Neuroscience. 86. 903-911 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe,M.: "Measurement of arginine carboxypeptidase-generating activity of adult plasma." Microbiol.Immunol.42. 393-397 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田公介: "進行性悪性腫瘍に対するLAK療法と局所ハイパーサーミアの併用療法" Biotherapy. 12. 80-82 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miwa,T.: "Molecular cloning of rat and mouse membrane cofactor protein (MCP, CD46) : preferential expression in testis and close linkage between the mouse Mcp and Cr2 genes on distal chromosome 1." Immunogenetics. 48. 363-371 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishikawa,K.: "Tissue distribution of the guinea-pig decay-acceierating factor." Immunology. 95. 302-307 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 〓onaka,M.: "A new repetitive sequence uniquely present in the decay-accelerating factor genes." Immunogenetics. 47. 246-255 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okada,H.: "The Complement System Membrane-bound inhibitors of C5b-9." Springer, 174-177 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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