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Design, Selection and Binding Mechanism of Bivalent Miniproteins Targeting Human Thrombin

  • Andy Ng
  • Jamshid Tanha
  • Saran Narang
  • Feng Ni
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Multilvalent molecular designs have emerged as an important tool for protein engineering and drug discovery complementary to the traditional methods of medicinal chemistry and recombinant antibody technology. Like antibodies, this new generation of molecules is particularly suited for the inhibition of difficult pharmaceutical targets such as protein-protein interactions. Unlike antibody engineering, the design of effective multivalent (or minimally bivalent) molecules is still wrought with trial and error, especially with regard to the selection of individual binding moieties and the choice of linking strategies. Using the thrombin system as an example, we aim to evolve a general approach for the design of protein-targeting bivalent polypeptides. Our design scheme involved the selection of binding moieties through screenings of relatively unsophisticated libraries, which often yield low-affinity, fast-dissociating hits. Through bivalency, however, we showed that these...

Keywords

Active Site Inhibitor Bivalent Binding Linker Moiety Avidity Effect Undesirable Protein 
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.

References

  1. 1.
    Tanha, J., Dubuc, G., Hirama, T., Narang, S.A., and MacKenzie, C.R. J. Immunol. Methods 263, 97–109 (2002).CrossRefGoogle Scholar
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    Su, Z., Vinogradova, A., Koutychenko, A., Tolkatchev, D. and Ni, F. Protein Eng. Des. Sel. 17, 647–657 (2004).CrossRefGoogle Scholar
  3. 3.
    Tolkatchev, D., Vinogradova, A. and Ni, F. Bioorg. Med. Chem. Lett. 15, 5120–5123 (2005).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Andy Ng
    • 1
  • Jamshid Tanha
    • 2
  • Saran Narang
    • 2
  • Feng Ni
    • 1
  1. 1.Biomolecular NMR and Protein Research, Biotechnology Research InstituteNational Research CouncilMontrealCanada
  2. 2.Institute for Biological SciencesNational Research CouncilOttawaCanada

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