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Updated: May 6, 2026
11:59
Competitive Genomic Screens of Barcoded Yeast Libraries
Published on: August 11, 2011
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Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking
Sara Linciano1, Ylenia Mazzocato1, Zhanna Romanyuk1
1Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Via Torino 155, 30172, Venice, Italy.
Nature Communications
|June 25, 2025
Summary
We developed a yeast display method to create and test diverse macrocyclic peptides. This approach efficiently identifies potent peptide drug candidates for various therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Macrocyclic peptides are promising drug candidates with favorable properties.
- In vitro evolution techniques like phage and mRNA display have limitations.
- Existing methods for macrocyclic peptide discovery require improvement.
Purpose of the Study:
- To develop a yeast display-based strategy for generating, screening, and characterizing disulfide-cyclized macrocyclic peptides.
- To overcome limitations of current in vitro evolution techniques.
- To identify novel macrocyclic peptide ligands with high binding affinity for therapeutic targets.
Main Methods:
- Development of a yeast display system for macrocyclic peptide generation and screening.
- Utilizing quantitative flow cytometry for real-time monitoring of millions of peptides.
- Employing X-ray crystallography to analyze ligand-target interactions.
Main Results:
- Successful generation and screening of structurally diverse disulfide-cyclized peptides.
- Identification of high-affinity ligands for five different protein targets.
- X-ray analysis revealed optimal shape complementarity and extensive interactions for a selected ligand, explaining its affinity and selectivity.
Conclusions:
- The yeast display approach provides a facile, quantitative, and cost-effective method for macrocyclic peptide discovery.
- This strategy enables rapid and efficient identification and characterization of genetically encoded peptide ligands.
- The developed method is suitable for discovering ligands against therapeutically relevant targets.
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