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

• Published in: Nature communications Vol. 12; no. 1; p. 4494
• Main Authors: Yang, Pei-Pei, Li, Yi-Jing, Cao, Yan, Zhang, Lu, Wang, Jia-Qi, Lai, Ziwei, Zhang, Kuo, Shorty, Diedra, Xiao, Wenwu, Cao, Hui, Wang, Lei, Wang, Hao, Liu, Ruiwu, Lam, Kit S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-07-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 49/75; 631/45/611; 631/92/507; 639/301/357/341; 639/638/541/966; 639/925/350/2093; Aqueous environments; Beads; Biocompatibility; Biomedical materials; Combinatorial analysis; Experimental methods; Fluorescence; Humanities and Social Sciences; Hydrophobicity; Libraries; multidisciplinary; Nanofibers; Nanoparticles; Nanotechnology; Pentapeptides; Peptides; Science; Science (multidisciplinary); Self-assembly
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24597-5

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.
Self-assembling peptides have a range of potential applications but developing self-assembling sequences can be challenging. Here, the authors report on a one-bead one-compound combinatorial library where fluorescence is used to detect the potential for self-assembly and identified candidates are evaluated.