4-Fluoroproline derivative peptides: effect on PPII conformation and SH3 affinity

Journal of Peptide Science : an Official Publication of the European Peptide Society
P RuzzaG Borin

Abstract

Eukaryotic signal transduction involves the assembly of transient protein-protein complexes mediated by modular interaction domains. Specific Pro-rich sequences with the consensus core motif PxxP adopt the PPII helix conformation upon binding to SH3 domains. For short Pro-rich peptides, little or no ordered secondary structure is usually observed before binding interactions. The association of a Pro-rich peptide with the SH3 domain involves unfavorable binding entropy due to the loss of rotational freedom on forming the PPII helix. With the aim of stabilizing the PPII helix conformation in the Pro-rich HPK1 decapeptide PPPLPPKPKF (P2), a series of P2 analogues was prepared, in which specific Pro positions were alternatively occupied by 4(S)- or 4(R)-4-fluoro-L-proline. The interactions of these peptides with the SH3 domain of the HPK1-binding partner HS1 were quantitatively analyzed by the NILIA-CD approach. A CD thermal analysis of the P2 analogues was performed to assess their propensity to adopt the PPII helix conformation. Contrary to our expectations, the K(d) values of the analogues were lower than that of the parent peptide P2. These results clearly show that the induction of a stable PPII helix conformation in short Pro...Continue Reading

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Citations

Feb 3, 2011·Amino Acids·Giuliano SiligardiArianna Donella-Deana
Aug 5, 2010·Journal of the American Chemical Society·Matthew D ShouldersRonald T Raines
Apr 13, 2011·The Journal of Biological Chemistry·Matthew D Shoulders, Ronald T Raines
Jun 23, 2016·Biophysical Journal·Veer S BhattJae-Hyun Cho
May 3, 2018·Chemical Communications : Chem Comm·Gert-Jan HofmanBruno Linclau
Sep 14, 2017·Molecular Medicine Reports·Qing ZhangHuilin Zhang
Mar 18, 2021·Beilstein Journal of Organic Chemistry·Vladimir KubyshkinNediljko Budisa
Oct 2, 2012·Organic Letters·Vladimir S KubyshkinIgor V Komarov

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