DNA-Encoded Noncanonical Substrate Library for Protease Profiling
文献类型：期刊论文
| 作者 | Zhang, Huiya2,3; Xing, Yuyu2,3; Yang, Yixuan4; Tang, Bixi4; Zong, Zhaoyun2; Li, Jia4 ; Zang, Yi5; Bogyo, Matthew1; Lu, Xiaojie4; Chen, Shiyu2,3
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| 刊名 | CHEMBIOCHEM
 |
| 出版日期 | 2024-11-04 |
| 页码 | 12 |
| 关键词 | Protease substrate DNA-encoded library Combinatorial peptide library High-throughput screening Covalent inhibitor Noncanonical peptide |
| ISSN号 | 1439-4227 |
| DOI | 10.1002/cbic.202400559 |
| 英文摘要 | Profiling the substrate sequence preferences of proteases is important for understanding both biological functions as well as for designing protease inhibitors. Several methods are available for profiling the sequence specificity of proteases. However, there is currently no rapid and high-throughput method to profile specificity of proteases for noncanonical substrates. In this study, we described a strategy to use a DNA-encoded noncanonical substrate library to identify the protease substrates composed of both canonical and noncanonical amino acids. This approach uses a DNA-encoded peptide library and introduces a biotin molecule at the N-terminus to immobilize the library on a solid support. Upon protease hydrolysis, the released DNA tag of the substrate peptides can be sequenced to identify the substrate structures. Using this approach, we profiled trypsin and fibroblast activation protein alpha and discovered noncanonical substrates that were more efficiently cleaved than the commonly used substrates. The identified substrates of FAP were further used to design corresponding covalent inhibitors containing non-canonical sequences with high potency for the target protease. Overall, our approach can aid in the development of new protease substrates and inhibitors. |
| WOS关键词 | ACTIVITY-BASED PROBES ; MATRIX METALLOPROTEINASES ; SELECTIVE INHIBITORS ; SPECIFICITY ; DISCOVERY ; DESIGN ; POTENT ; IV |
| 资助项目 | Distinguished Young Scholars Program and the General Program of the National Natural Science Foundation of China ; Distinguished Young Scholars Program[22477128] ; General Program of the National Natural Science Foundation of China |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| WOS记录号 | WOS:001357426900001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/314512]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Shiyu |
| 作者单位 | 1.Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Biotech Drug Res Ctr, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Lin Gang Lab, 319 Yue Yang Rd, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Huiya,Xing, Yuyu,Yang, Yixuan,et al. DNA-Encoded Noncanonical Substrate Library for Protease Profiling[J]. CHEMBIOCHEM,2024:12. |
| APA | Zhang, Huiya.,Xing, Yuyu.,Yang, Yixuan.,Tang, Bixi.,Zong, Zhaoyun.,...&Chen, Shiyu.(2024).DNA-Encoded Noncanonical Substrate Library for Protease Profiling.CHEMBIOCHEM,12. |
| MLA | Zhang, Huiya,et al."DNA-Encoded Noncanonical Substrate Library for Protease Profiling".CHEMBIOCHEM (2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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