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Effect of 4-Fluoro-L-proline on the SH3 Binding Affinity

  • Paolo Ruzza
  • Chiara Rubini
  • Giuliano Siligardi
  • Rohanah Hussain
  • Andrea Calderan
  • Andrea Guiotto
  • Luca Cesaro
  • Anna M. Brunati
  • Arianna Donella-Deana
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Short proline-rich peptides corresponding to well-known SH3 ligands exhibit little or no secondary structure before their binding to the cognate protein-targets. Under these conditions the association of a proline-rich peptide with the SH3 domain indicates unfavorable binding entropy, likely resulting from a loss of rotational freedom on the formation of the PPII helix.

With the aim of stabilizing the PPII helix conformation in SH3 binding motifs we replaced the proline residues of the HPK1 proline-rich decapeptide, PPPLPPKPKF ( P2), either with the 4-R-fluoro-L-proline ( FPro) or with the 4-S-fluoro-L-proline ( fPro) [ 1] at different i, i+ 3 positions (Table 1). The interactions of the fluoro-proline peptides with the SH3 domain of the protein cortactin were analyzed quantitatively by non-immobilized ligand interactions assay by circular dichroism (NILIA-CD). The conformation of each peptide in both aqueous and organic solvents was investigated as a function of temperature...

Keywords

Negative Band Parent Peptide PPII Helix Protein Cortactin PPII Conformation 
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.
    Horng, J. C. and Raines, R. T. Protein Sci. 15, 74–83 (2006).CrossRefGoogle Scholar
  2. 2.
    Mutter, M., et al. Biopolymers 51, 121–128 (1999).CrossRefGoogle Scholar
  3. 3.
    Siligardi, G., et al. J. Biol. Chem. 277, 20151–20159 (2002).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Paolo Ruzza
    • 1
  • Chiara Rubini
    • 1
  • Giuliano Siligardi
    • 2
  • Rohanah Hussain
    • 2
  • Andrea Calderan
    • 1
  • Andrea Guiotto
    • 1
  • Luca Cesaro
    • 3
  • Anna M. Brunati
    • 3
  • Arianna Donella-Deana
    • 3
  1. 1.Padua UnitCNR Institute of Biomolecular ChemistryPaduaItaly
  2. 2.Chilton, DidcotDiamond Light Source, Diamond HouseOxfordshireUK
  3. 3.University of PaduaDepartment of Biological ChemistryPaduaItaly

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