A phage display-based strategy for the de novo creation of disulfide-constrained and isomer-free bicyclic peptide affinity reagents

We report a phage-screening strategy for the development of bicyclic peptide ligands constrained with two sterically different and isomerically forbidden noncanonical disulfide bridges without elaborate chemical modifications and recourses to genetic code reprogramming.

Download Full-text

Development and Application of Computational Methods in Phage Display Technology

Current Medicinal Chemistry ◽

10.2174/0929867325666180629123117 ◽

2020 ◽

Vol 26 (42) ◽

pp. 7672-7693 ◽

Cited By ~ 3

Author(s):

Bifang He ◽

Anthony Mackitz Dzisoo ◽

Ratmir Derda ◽

Jian Huang

Keyword(s):

Phage Display ◽

Computational Methods ◽

Peptide Ligands ◽

Next Generation ◽

Phage Display Technology ◽

Next Generation Sequencing Technology ◽

Screening Experiments ◽

Display Technology ◽

Comprehensive Search ◽

Generation Sequencing

Background: Phage display is a powerful and versatile technology for the identification of peptide ligands binding to multiple targets, which has been successfully employed in various fields, such as diagnostics and therapeutics, drug-delivery and material science. The integration of next generation sequencing technology with phage display makes this methodology more productive. With the widespread use of this technique and the fast accumulation of phage display data, databases for these data and computational methods have become an indispensable part in this community. This review aims to summarize and discuss recent progress in the development and application of computational methods in the field of phage display. Methods: We undertook a comprehensive search of bioinformatics resources and computational methods for phage display data via Google Scholar and PubMed. The methods and tools were further divided into different categories according to their uses. Results: We described seven special or relevant databases for phage display data, which provided an evidence-based source for phage display researchers to clean their biopanning results. These databases can identify and report possible target-unrelated peptides (TUPs), thereby excluding false-positive data from peptides obtained from phage display screening experiments. More than 20 computational methods for analyzing biopanning data were also reviewed. These methods were classified into computational methods for reporting TUPs, for predicting epitopes and for analyzing next generation phage display data. Conclusion: The current bioinformatics archives, methods and tools reviewed here have benefitted the biopanning community. To develop better or new computational tools, some promising directions are also discussed.

Download Full-text

Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5

Molecules ◽

10.3390/molecules26051225 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1225

Author(s):

Jiawen Cao ◽

Tiantian Fan ◽

Yanlian Li ◽

Zhiyan Du ◽

Lin Chen ◽

...

Keyword(s):

Phage Display ◽

Cyclic Peptide ◽

Protein Complexes ◽

Peptide Ligands ◽

Phage Library ◽

Cancer Drug ◽

Protein Protein Interaction ◽

Phage Display Technique ◽

Peptide Mimic ◽

Human Proteins

WD40 is a ubiquitous domain presented in at least 361 human proteins and acts as scaffold to form protein complexes. Among them, WDR5 protein is an important mediator in several protein complexes to exert its functions in histone modification and chromatin remodeling. Therefore, it was considered as a promising epigenetic target involving in anti-cancer drug development. In view of the protein–protein interaction nature of WDR5, we initialized a campaign to discover new peptide-mimic inhibitors of WDR5. In current study, we utilized the phage display technique and screened with a disulfide-based cyclic peptide phage library. Five rounds of biopanning were performed and isolated clones were sequenced. By analyzing the sequences, total five peptides were synthesized for binding assay. The four peptides are shown to have the moderate binding affinity. Finally, the detailed binding interactions were revealed by solving a WDR5-peptide cocrystal structure.

Download Full-text