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Side chain-to-Side chain Cyclization by Intramolecular Click Reaction - Building Blocks, Solid Phase Synthesis and Conformational Characterization

  • Sonia Cantel
  • Jose A. Halperin
  • Michael Chorev
  • Mario Scrima
  • Anna M. D'Ursi
  • Jay J. Levy
  • Richard D. DiMarchi
  • Alexandra Le Chevalier
  • Paolo Rovero
  • Anna M. Papini
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Side chain-to-side chain cyclization is frequently employed to stabilize and select specific conformations and to reduce susceptibility toward proteolytic degradation. Among the numerous modes of cyclization bioisosteric modifications that can be accomplished without elaborate orthogonal protection schemes are of great interest. The recently introduced CuI-catalyzed azide—alkyne 1,3-dipolar Huisgen's cycloaddition [1] as a prototypic “Click reaction” [2] presented a promising opportunity to develop a new paradigm for intramolecular side chain-to-side chain cyclization. The inherent high energetics, chemical selectivity, and the demonstrated bioorthogonal characteristics of the azide and alkynyl functions, as well as the proteolytic stability, and the peptidomimetic nature of the cycloaddition product, the 1,4-disubstituted [1,2,3]triazolyl moiety, suggest that 1,4-bridged [1,2,3]triazolyl-mediated side chain-to side chain cyclization could offer an interesting mode of...

Keywords

Cyclic Peptide Lactam Ring Cycloaddition Product Chain Cyclization Triazole Moiety 
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

The work was funded by FIRB internazionalizzazione 2005 RBIN04TWKN.

References

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    Maretto, et al. Biochemistry 36, (11), 3300–7, 1997.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Sonia Cantel
    • 1
    • 2
  • Jose A. Halperin
    • 1
    • 2
  • Michael Chorev
    • 1
    • 2
  • Mario Scrima
    • 3
  • Anna M. D'Ursi
    • 3
  • Jay J. Levy
    • 4
  • Richard D. DiMarchi
    • 4
  • Alexandra Le Chevalier
    • 5
  • Paolo Rovero
    • 5
  • Anna M. Papini
    • 5
  1. 1.Laboratory for Translational ResearchHarvard Medical SchoolCambridgeUSA
  2. 2.Department of MedicineBrigham and Women's HospitalBostonUSA
  3. 3.Dipartimento di Scienze FarmaceuticheVia Ponte Don Melillo 11CSalernoItaly
  4. 4.Department of ChemistryIndiana UniversityBloomingtonUSA
  5. 5.Laboratorio di Chimica dei PeptidiDipartimento di Chimica Organica “Ugo Schiff”Sesto F.no (Firenze)Italy

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