Rapid discovery of self-assembling peptides with one-bead one-compound peptide library

Pei-Pei Yang, Yi-Jing Li, Yan Cao, Lu Zhang, Jia-Qi Wang, Ziwei Lai, Kuo Zhang, Diedra Shorty, Wenwu Xiao, Hui Cao, Lei Wang (), Hao Wang (), Ruiwu Liu () and Kit S. Lam ()
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Pei-Pei Yang: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Yi-Jing Li: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Yan Cao: Shenzhen University
Lu Zhang: University of California Davis
Jia-Qi Wang: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Ziwei Lai: Shenzhen University
Kuo Zhang: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Diedra Shorty: University of California Davis
Wenwu Xiao: University of California Davis
Hui Cao: University of Science and Technology Beijing
Lei Wang: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Hao Wang: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun
Ruiwu Liu: University of California Davis
Kit S. Lam: University of California Davis

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract Self-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.

Date: 2021
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DOI: 10.1038/s41467-021-24597-5

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