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Development of a Novel Fusion Inhibitor against T-20-resistant HIV-1

  • Shinya Oishi
  • Saori Ito
  • Hiroki Nishikawa
  • Michinori Tanaka
  • Hiroaki Ohno
  • Akira Otaka
  • Kazuki Izumi
  • Eiichi Kodama
  • Masao Matsuoka
  • Nobutaka Fujii
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

T-20 (also known as Fuzeon and enfuvirtide) is a potent human immunodeficiency virus-1 (HIV-1) fusion inhibitory peptide derived from a C-terminal heptad repeat (C-HR) of envelope glycoprotein gp41 [1]. Although even multi-drug-resistant HIV variants are effectively suppressed by T-20-containing regimens in the treatment of HIV/AIDS, it has been reported that T-20-resistant HIV strains can emerge after prolonged therapy [2].

Another C-HR-derived peptide C34 also exhibits potent anti-HIV activity by inhibiting the fusogenic six-helical bundle formation. It has been revealed that binding of C34 with the coiled-coil structure of an N-terminal heptad repeat (N-HR) occurs in α helix conformations, while the binding mode of T-20 remains ambiguous [3]. Previously, we have demonstrated that replacement of the i, i + 4 residues at solvent-accessible sites of C34 with Glu or Lys leads to stabilization of the six-helical bundle by potential salt-bridge formation of Glu—Lys pairs [4]....

Keywords

Helix Structure Fusion Inhibitor Envelope Glycoprotein Gp41 Original Amino Acid Cosmosil 5C18 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and Health and Labour Sciences Research Grants (Research on HIV/AIDS). H.N. is grateful for Research Fellowships from the JSPS for Young Scientists.

References

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Shinya Oishi
    • 1
  • Saori Ito
    • 1
  • Hiroki Nishikawa
    • 1
  • Michinori Tanaka
    • 1
  • Hiroaki Ohno
    • 1
  • Akira Otaka
    • 1
  • Kazuki Izumi
    • 2
  • Eiichi Kodama
    • 2
  • Masao Matsuoka
    • 2
  • Nobutaka Fujii
    • 1
  1. 1.Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Institute for Virus ResearchKyoto UniversityKyotoJapan

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