Related Experiment Video
Updated: Jun 15, 2025
08:31
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
5.0K
Proximity-driven site-specific cyclization of phage-displayed peptides
Libby Brown1,2, Aldrin V Vidal1, Ana Laura Dias3
1Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Nature Communications
|August 24, 2024
Summary
We developed a novel cyclopropenone linker for site-specific peptide cyclization in phage display. This method enhances peptide stability and binding affinity, creating diverse libraries for selecting high-affinity binders.
Area of Science:
- Biochemistry
- Chemical Biology
- Molecular Biology
Background:
- Peptide cyclization enhances stability, permeability, and binding affinity.
- Disulfide bond replacement with linkers is common for cyclizing phage-displayed peptides.
- Existing linkers lack selectivity for specific cysteine residues in phage display systems.
Purpose of the Study:
- To develop a selective chemical linker for peptide cyclization in phage display.
- To create stable, diverse phage display libraries for selecting high-affinity peptide binders.
Main Methods:
- Development of a cyclopropenone-based, proximity-driven chemical linker.
- Application of the linker for site-specific cyclization of synthetic peptides, phage-coat protein fusions, and phage-displayed peptides.
- Construction and utilization of phage display libraries for selection experiments.
Main Results:
- The cyclopropenone linker efficiently and site-specifically cyclizes peptides without affecting phage infectivity.
- Stable and highly diverse phage display libraries were constructed.
- High-affinity cyclic peptide binders were selected against streptavidin and αvβ3 integrin.
Conclusions:
- The cyclopropenone linker offers a selective and efficient method for peptide cyclization in phage display.
- This strategy enables the generation of improved peptide-based therapeutics and research tools.
- The developed libraries are valuable for discovering novel peptide binders with enhanced properties.
Related Concept Videos
02:53Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
01:30Lytic Cycle of Bacteriophages
70.5K
Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...
70.5K
00:43Lysogenic Cycle of Bacteriophages
62.0K
In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
62.0K