Tailored Cross‐β Assemblies Establish Peptide "Dominos" Structures for Anchoring Undruggable Pharmacophores. (17th November 2022)

• Record Type: Journal Article
• Authors: Zhang, Limin; Li, Mengzhen; Wang, Minxuan; Li, Lingyun; Guo, Mingmei; Ke, Yubin; Zhou, Peng; Wang, Weizhi
• Is Part Of: Angewandte Chemie. Volume 134:Number 51(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-17
• Subjects: Dominos -- PD-L1 -- Peptides -- Self-Assembly -- β-Sheets; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202212527
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: β‐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 β‐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‐L1 was demonstrated. This study successfully established the structure‐function relationship of β‐sheets assemblies and has positive implications on the rational design of peptide assemblies that possess recognition abilities. Abstract : By adjusting the solvent‐accessible surface area of the peptide chain, the tilt angle of the β‐sheets in the self‐assembly could be manipulated to form a collapsed‐domino‐like structure, resulting in a controllable display of the active sites for PD‐L1 recognition.