Rapid Discovery of Self-Assembling Peptides with One-Bead One-Compound Peptide Libraries

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 identified eight pentapeptides, all of which were able to self-assemble into nanoparticles or nanofibers. Some of them were able to interact with and taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This novel but very simple screening strategy, has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.