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Design and Synthesis of Backbone Cyclic Phosphopeptides: The IκB Model

  • Nir Qvit
  • Ada Hatzubai
  • Deborah E. Shalev
  • Yinon Ben-Neriah
  • Chaim Gilon
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

We present the development and synthesis of a backbone cyclic (BC) phosphoserine-containing library. For our model, we used the conserved sequence derived from Inhibitor kappa B (IκB) that inhibits the interaction between IκB and the β-transduction repeat-containing protein (β-TrCp). Backbone cyclization is a method for conferring metabolic stability and enhanced bioavailability on a chosen biologically active sequence. Cycloscan is a method in which a library is designed using a single parent sequence but differing BC ring closures to allow the biologically active sequence conformational diversity. A selective and metabolically stable BC peptide may be identified from such a library [1]. Phosphopeptides are potential inhibiters of the kinome, the subset of the genome consisting of the protein kinase genes [2], but are synthetically challenging.

We applied the backbone cyclization strategy to find a peptide that inhibits nuclear factor-kappa B (NF-κB). NF-κB is a latent...

Keywords

Binding Pocket Secondary Amine Cyclic Peptide Peptide Library Protein Kinase Gene 
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

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Nir Qvit
    • 1
  • Ada Hatzubai
    • 2
  • Deborah E. Shalev
    • 3
  • Yinon Ben-Neriah
    • 2
  • Chaim Gilon
    • 1
  1. 1.Department of Organic ChemistryThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.The Lautenberg Center for ImmunologyThe Hebrew University-Hadassah Medical SchoolJerusalem
  3. 3.The Wolfson Centre for Applied Structural BiologyThe Hebrew University of JerusalemJerusalemIsrael

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