Dataset Information

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

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.

SUBMITTER: Cao J

PROVIDER: S-EPMC7956166 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Cao Jiawen J Fan Tiantian T Li Yanlian Y Du Zhiyan Z Chen Lin L Wang Ying Y Wang Xin X Shen Jingkang J Huang Xun X Xiong Bing B Cao Danyan D

Molecules (Basel, Switzerland) 20210225 5

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 ...[more]

PMID: 33668971

Similar Datasets

Project description:Peptide therapeutics are robust and promising molecules for treating diverse disease conditions. These molecules can be developed from naturally occurring or mimicking native peptides, through rational design and peptide libraries. We developed a new platform for the rapid screening of the peptide therapeutics for disease targets. In the course of the study, we aimed to employ our platform to screen a new generation of peptide therapeutic candidates against aggregation-prone protein targets. Two peptide drug candidates were screened for protein aggregation-prone diseases, namely, Parkinson's and Alzheimer's diseases. Currently, there are several therapeutic applications that are only effective in masking or slowing down symptom development. Nonetheless, different approaches are being developed for inhibiting amyloid aggregation in the secondary nucleation phase, which is critical for amyloid fibril formation. Instead of targeting secondary nucleated protein structures, we tried to inhibit the aggregation of monomeric amyloid units as a novel approach for halting the disease condition. To achieve this, we combined yeast surface display and phage display library platforms. We expressed α-synuclein, amyloid β40, and amyloid β42 on the yeast surface, and we selected peptides by using phage display library. After iterative biopanning cycles optimized for yeast cells, several peptides were selected for interaction studies. All of the peptides have been used for in vitro characterization methods, which are quartz crystal microbalance-dissipation (QCM-D) measurement, atomic force microscopy (AFM) imaging, dot-blotting, and ThT assay, and some of them have yielded promising results in blocking fibrillization. The rest of the peptides, although, interacted with amyloid units which made them usable as a sensor molecule candidate. Therefore, peptides selected by yeast surface display and phage display library combination are good choice for diverse disease-prone molecule inhibition, particularly those inhibiting fibrillization. Additionally, these selected peptides can be used as drugs and sensors to detect diseases quickly and halt disease progression.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets