Related Experiment Video
Updated: Aug 2, 2026
Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
Identification of novel mdm2 binding peptides by phage display
V Böttger1, A Böttger, S F Howard
1Cancer Research Campaign Laboratories, University of Dundee, Scotland, UK.
Abstract:
The oncogene mdm2 and its human homologue hdm2 bind to the tumour suppressor protein p53 and inactivate its function as a transcription factor. This has been implied as a possible mechanism for cancer development in several tumours including human sarcomas. The mdm2-p53 interaction is therefore a much persued target for the development of anti-cancer drugs. In order to find novel high affinity ligands for hdm2 which would interfere with its binding to p53 we screened phage display peptide libraries for mdm2 binding phage. We found a series of 12 and 15mer peptides which interact strongly with hdm2. The peptide sequences show striking homology with the previously established mdm2 binding site on p53, confirming that the peptide defined 18TFSDLW23 region is crucial for the interaction but that contact between the two molecules extends to position L26 on p53. Free synthetic peptides derived from the phage selected sequences proved to be up to 100 times stronger inhibitors of the p53-mdm2 interaction than the p53 derived wt-peptide in several ELISA-assays. This illustrates the potency of phage display libraries in the search for new peptide based lead structures designed to mimic or inhibit therapeutically important protein-protein interactions.
Insights
Researchers discovered novel peptides that strongly inhibit the mdm2-p53 interaction, a key target in cancer drug development. These peptides show potential as new anti-cancer therapeutics by blocking this crucial protein binding.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The oncogene mdm2/hdm2 protein inactivates the tumor suppressor p53, a mechanism implicated in various cancers.
- The mdm2-p53 interaction is a significant target for developing novel anti-cancer drugs.
Purpose of the Study:
- To identify high-affinity ligands that disrupt the mdm2-p53 binding interaction.
- To explore the potential of phage display libraries for discovering peptide-based therapeutic leads.
Main Methods:
- Screening of phage display peptide libraries to identify mdm2-binding phage.
- Characterization of peptide sequences and their homology to the p53 binding site.
- Inhibition assays (ELISA) to quantify the potency of synthetic peptides.
Main Results:
- Identified 12mer and 15mer peptides with strong binding affinity for hdm2.
- Confirmed the crucial role of the p53 18TFSDLW23 region and extended contact to L26.
- Phage-derived synthetic peptides demonstrated up to 100-fold greater inhibition of p53-mdm2 interaction compared to wild-type p53 peptides.
Conclusions:
- Phage display is a powerful tool for discovering peptide inhibitors of protein-protein interactions.
- Novel peptide ligands can effectively inhibit the mdm2-p53 interaction, offering a promising avenue for cancer therapy.
- These findings highlight the therapeutic potential of targeting protein-protein interactions with peptide-based drugs.
