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  • Research Article
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Computer-assisted rational design of immunosuppressive compounds

Nature Biotechnology volume 16, pages 748–752 (1998)Cite this article

Abstract

We describe the rational design of immunosuppressive peptides without relying on information regarding their receptors or mechanisms of action. The design strategy uses a variety of topological and shape descriptors in combination with an analysis of molecular dynamics trajectories for the identification of potential drug candidates. This strategy was applied to the development of immunosuppressive peptides with enhanced potency. The lead compounds were peptides, derived from the heavy chain of HLA class I, that modulate immune responses in vitro and in vivo. In particular, a peptide derived from HLA-B2702, amino acids 75–84 (2702.75–84) prolonged skin and heart allograft survival in mice. The biological activity of the rationally designed peptides was tested in a heterotopic mouse heart allograft model. The molecule predicted to be most potent displayed an immunosuppressive activity approximately 100 times higher than the lead compound.

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Author notes

  1. Roger Lahana: (e-mail: rlahana@syntem.eerie.fr).

  2. Gérard Grassy and Bernard Calas: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre de Biochimie Structural. UMR CNRS 9955, INSERM U414, Faculté de Pharmacie, 15 Av. Charles Flahault, 34060, Montpellier, France

    Gérard Grassy

  2. CRBM, UPR 9008 CNRS, 34000, Montpellier, France

    Bernard Calas

  3. Synt:em, Parc Scientifique Georges Besse, 30000, Nîmes, France

    Abdelaziz Yasri, Roger Lahana & Michel Kaczorek

  4. SangStat Medical Corporation, Menlo Park, CA

    Jacky Woo, Suhasini Iyer, Robert Floc'h & Roland Buelow

Authors
  1. Gérard Grassy
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  8. Robert Floc'h
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  9. Roland Buelow
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Grassy, G., Calas, B., Yasri, A. et al. Computer-assisted rational design of immunosuppressive compounds. Nat Biotechnol 16, 748–752 (1998). https://doi.org/10.1038/nbt0898-748

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