Journal
MOLECULES
Volume 26, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/molecules26051225
Keywords
phage display; biopanning; WDR5; cocrystal structure
Funding
- National Natural Science Foundation of China [81773572, 91853126]
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This study utilized phage display technique to discover new peptide-mimic inhibitors of WDR5, and four peptides with moderate binding affinity were identified. The detailed binding interactions were revealed by solving a WDR5-peptide cocrystal structure.
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.
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