Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5
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...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/5/1225 |
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| author | Jiawen Cao Tiantian Fan Yanlian Li Zhiyan Du Lin Chen Ying Wang Xin Wang Jingkang Shen Xun Huang Bing Xiong Danyan Cao |
| author_facet | Jiawen Cao Tiantian Fan Yanlian Li Zhiyan Du Lin Chen Ying Wang Xin Wang Jingkang Shen Xun Huang Bing Xiong Danyan Cao |
| author_sort | Jiawen Cao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T00:32:35Z |
| format | Article |
| id | doaj.art-82d28c4d7f94455f8c66d08843f0a02e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:32:35Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-82d28c4d7f94455f8c66d08843f0a02e2023-12-11T18:25:09ZengMDPI AGMolecules1420-30492021-02-01265122510.3390/molecules26051225Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5Jiawen Cao0Tiantian Fan1Yanlian Li2Zhiyan Du3Lin Chen4Ying Wang5Xin Wang6Jingkang Shen7Xun Huang8Bing Xiong9Danyan Cao10Department of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaDepartment of College of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, ChinaWD40 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.https://www.mdpi.com/1420-3049/26/5/1225phage displaybiopanningWDR5cocrystal structure |
| spellingShingle | Jiawen Cao Tiantian Fan Yanlian Li Zhiyan Du Lin Chen Ying Wang Xin Wang Jingkang Shen Xun Huang Bing Xiong Danyan Cao Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 Molecules phage display biopanning WDR5 cocrystal structure |
| title | Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 |
| title_full | Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 |
| title_fullStr | Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 |
| title_full_unstemmed | Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 |
| title_short | Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5 |
| title_sort | phage display based discovery and characterization of peptide ligands against wdr5 |
| topic | phage display biopanning WDR5 cocrystal structure |
| url | https://www.mdpi.com/1420-3049/26/5/1225 |
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