Screening and optimization of phage display cyclic peptides against the WDR5 WBM site
文献类型：期刊论文
| 作者 | Song, Lingyu1,2; Cao, Jiawen1,2; Chen, Lin2; Du, Zhiyan2; Zhang, Naixia1,3 ; Cao, Danyan2; Xiong, Bing1,2,4
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| 刊名 | RSC MEDICINAL CHEMISTRY
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| 出版日期 | 2023-08-17 |
| 页码 | 10 |
| DOI | 10.1039/d3md00288 |
| 通讯作者 | Cao, Danyan(caody@simm.ac.cn) ; Xiong, Bing(bxiong@simm.ac.cn) |
| 英文摘要 | Of the various WD40 family proteins, WDR5 is a particularly important multifunctional adaptor protein that can bind to several protein complexes to regulate gene activation, so it was considered as a promising epigenetic target in anti-cancer drug development. Despite many inhibitors having been discovered directing against the arginine-binding cavity in WDR5 called the WIN site, the side hydrophobic cavity called the WBM site receives rather scant attention. Herein, we aim to obtain novel WBM-targeted peptidic inhibitors with high potency and selectivity. We employed two improved biopanning approaches with a disulfide-constrained cyclic peptide phage library containing 7 randomized residues and identified several peptides with micromole binding activity by docking and binding assay. To further optimize the stability and activity, 9 thiol-reactive chemical linkers were utilized in the cyclization of the candidate peptide DH226027, which had good binding affinity. This study provides an effective method to discover potent peptides targeting protein-protein interactions and highlights a broader perspective of peptide-mimic drugs. We reported two improved screenings based on the phage display technique to discover novel peptidic inhibitors against the WDR5 WBM site, and the optimized cyclic peptide CYC3 was acquired, which could be subjected to further biological evaluation. |
| WOS关键词 | HISTONE H3 ; COMPLEX ; RECOGNITION ; CYCLIZATION ; SCAFFOLDS ; SELECTION ; BINDING |
| 资助项目 | This work was supported by the National Natural Science Foundation of China (82173658, 82373720).[82373720] ; National Natural Science Foundation of China ; [82173658] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001055798300001 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307049]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Cao, Danyan; Xiong, Bing |
| 作者单位 | 1.Univ Chinese Acad Sci, Dept Coll Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, Lingyu,Cao, Jiawen,Chen, Lin,et al. Screening and optimization of phage display cyclic peptides against the WDR5 WBM site[J]. RSC MEDICINAL CHEMISTRY,2023:10. |
| APA | Song, Lingyu.,Cao, Jiawen.,Chen, Lin.,Du, Zhiyan.,Zhang, Naixia.,...&Xiong, Bing.(2023).Screening and optimization of phage display cyclic peptides against the WDR5 WBM site.RSC MEDICINAL CHEMISTRY,10. |
| MLA | Song, Lingyu,et al."Screening and optimization of phage display cyclic peptides against the WDR5 WBM site".RSC MEDICINAL CHEMISTRY (2023):10. |
入库方式： OAI收割
来源：上海药物研究所
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