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Identifying Protein-protein Interaction Sites Using Peptide Arrays
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Screening for Selective Protein Inhibitors by Using the IANUS Peptide Array.

Frank Erdmann1,2, Erik Prell1,3, Günther Jahreis1

  • 1Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120, Halle/Saale, Germany.

Chembiochem : a European Journal of Chemical Biology
|February 8, 2018
PubMed
Summary

Researchers developed a cell-permeable peptidic inhibitor using a novel peptide array. This inhibitor effectively blocks calcineurin-mediated NFAT dephosphorylation and nuclear translocation in T-cells.

Keywords:
calcineurinfluorescenceinhibitorsmicroarrayspeptidesprotein-protein interactions

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Area of Science:

  • Immunology
  • Molecular Biology
  • Drug Discovery

Background:

  • Calcineurin (CaN) is a key phosphatase involved in T-cell activation.
  • Nuclear factor of activated T-cells (NFAT) dephosphorylation by CaN is crucial for T-cell signaling.
  • Targeting CaN-NFAT pathway is a strategy for immunosuppression.

Purpose of the Study:

  • To develop a novel cell-permeable peptidic inhibitor of calcineurin (CaN).
  • To investigate the inhibitor's ability to block nuclear factor of activated T-cells (NFAT) dephosphorylation and translocation.
  • To utilize a template-assisted IANUS peptide array for inhibitor development.

Main Methods:

  • Development of a peptidic inhibitor using a template-assisted IANUS peptide array.
  • Assessment of cell permeability of the developed peptide.
  • Evaluation of the inhibitor's effect on the translocation of a green fluorescent protein-NFAT fusion protein (GFP-NFAT) into the nucleus.

Main Results:

  • A cell-permeable peptidic inhibitor of calcineurin was successfully developed.
  • The inhibitor demonstrated the ability to block CaN-mediated NFAT dephosphorylation.
  • The peptide effectively inhibited the nuclear translocation of GFP-NFAT in stimulated cells.

Conclusions:

  • The novel peptidic inhibitor is a promising agent for targeting the CaN-NFAT pathway.
  • The IANUS peptide array is an effective platform for developing cell-permeable peptide inhibitors.
  • This inhibitor has potential therapeutic applications in T-cell mediated immune responses.