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Updated: Jan 22, 2026

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

Published on: September 30, 2019

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Protein Chemical Synthesis Combined with Mirror-Image Phage Display Yields d-Peptide EGF Ligands that Block the

Cristina Díaz-Perlas1, Monica Varese1, Salvador Guardiola1

  • 1Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.

Chembiochem : a European Journal of Chemical Biology
|July 4, 2019
PubMed

Insights

Researchers developed protease-resistant peptides to inhibit cancer-driving epidermal growth factor (EGF) signaling. These novel d-peptides show potential for new cancer therapies by blocking EGF-EGFR interactions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • The epidermal growth factor (EGF) pathway is frequently overactive in various cancers, making it a significant therapeutic target.
  • Existing drugs targeting the EGF receptor (EGFR) often face rapid tumor resistance.
  • Alternative strategies using small molecules and peptides targeting EGF have shown limited success.

Purpose of the Study:

  • To discover protease-resistant peptides capable of inhibiting the EGF-EGFR interaction using mirror-image phage display technology.
  • To develop novel therapeutic agents for cancer treatment by targeting the EGF pathway.

Main Methods:

  • Chemical synthesis of the enantiomeric protein d-EGF.
  • Selection of binding sequences using two phage-display peptide libraries against d-EGF.
  • Confirmation of d-peptide binding to natural EGF using surface acoustic waves (SAWs).
  • Structural analysis of EGF-peptide interactions using high-field NMR spectroscopy.

Main Results:

  • Identified a potent EGF binder, d-PI_4, which interacts with a region overlapping the EGFR binding interface.
  • Demonstrated that d-PI_4 effectively disrupts the EGF-EGFR interaction.
  • Confirmed the protease-resistant nature of the discovered d-peptides.

Conclusions:

  • Mirror-image phage display is an effective method for discovering protease-resistant peptides.
  • The identified peptide d-PI_4 shows promise for inhibiting EGF-EGFR signaling.
  • This approach offers a straightforward strategy for developing new peptide-based cancer therapeutics.
Keywords:
EGF receptorepidermal growth factormirror-image phage displaypeptide inhibitorprotein-protein interaction

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