期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 61, 期 51, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202212527
关键词
Dominos; PD-L1; Peptides; Self-Assembly; beta-Sheets
资金
- National Natural Science Foundation of China
- Beijing Natural Science Foundation
- Beijing Institute of Technology Research Fund Program for Young Scholars, National Natural Science Foundation of China
- Chinese Postdoctoral Science Foundation
- [22074006]
- [2222029]
- [51904322]
- [2021M693205]
Bola-like peptides were obtained through de novo design and combinatorial chemical screening, resulting in assemblies with different tilt angles and active sites by regulating the solvent-accessible surface area of the peptide chain. The structure-activity relationship of the optimized peptide system was established and its ability to target a specific protein was demonstrated. This study successfully established the structure-function relationship of beta-sheet assemblies and has implications for the rational design of peptide assemblies with recognition abilities.
beta-sheets have the ability to hierarchically stack into assemblies, and much effort has been spent on designing different peptides to regulate their assembly behaviors. Although the progress is remarkable, it remains challenging to manipulate them in a controllable way for achieving both tailored structures and specific functions. In this study, we obtained bola-like peptides using de novo design and combinatorial chemical screening. By regulating the solvent-accessible surface area of the peptide chain, a series of assemblies with different tilt angles and active sites of the beta-sheet were obtained, resembling collapsed dominos. The structure-activity relationship of the optimized peptide NQ40 system was established and its ability to target the PD-Ll was demonstrated. This study successfully established the structure-function relationship of beta-sheets assemblies and has positive implications on the rational design of peptide assemblies that possess recognition abilities.
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