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Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5
- Source :
- Molecules, Molecules, Vol 26, Iss 1225, p 1225 (2021), Volume 26, Issue 5
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Phage display
cocrystal structure
WDR5
Pharmaceutical Science
Biopanning
Ligands
Peptides, Cyclic
Chromatin remodeling
Article
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
0302 clinical medicine
lcsh:Organic chemistry
Peptide Library
Drug Discovery
Humans
Epigenetics
Physical and Theoretical Chemistry
biopanning
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
biology
Chemistry
Ligand binding assay
Organic Chemistry
Intracellular Signaling Peptides and Proteins
Cyclic peptide
Histone
Biochemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
phage display
Protein Binding
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Switzerland)
- Accession number :
- edsair.doi.dedup.....2a21898966b53f6df26f50a6f66be1a7