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

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.

Ophthalmic Solution of Smart Supramolecular Peptides to Capture Semaphorin 4D against Diabetic Retinopathy

“…The OBOC combinatorial library was constructed through combinational synthesis using seven different natural amino acids as building blocks. [ 15 ] Since one TentaGel S resin bead contains one peptide, the OBOC combinatorial library has a theoretical diversity of 18^7 coding peptides.…”

“…Peptides with structural and biological functions have been widely used for disease therapeutics. [ 15 , 16 , 17 ] Here, we report the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing sSema 4D ( Figure 1 ). The sSema4D targeting SSP eye drops, SSP‐1 and SSP‐2, are based on one‐bead‐one‐compound (OBOC) combinatorial peptide library and “in vivo self‐assembly” concept.…”

Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

“…In another work, Li et al focused on the relationship between the chemical structures of peptides and their albitites to form hydrogels, applying machine learning to generate a hydrogel library with more than 2,000 self-assembling dipeptides (Li F. et al, 2019). Besides computational simulations (Moitra et al, 2017), Yang et al recently capped a hydrophobicitysensitive probe, the nitro-1,2,3-benzoxadiazole (NBD), to the N-terminus of peptides on beads in the OBOC library, achieving the rapid screening of self-assembling pentapeptides experimentally (Yang et al, 2021). biomarker-targeting, enzyme-response, and treatment makes the self-assembling peptides as candidates for functional nanomaterials and smart nanomedicines more than scaffolds in hydrogels.…”

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis

“…29 In recent years, the development of biomimetic binding-induced fibrillogenesis (BIF) peptides showed great significance in the fight against cancer and bacteria. 30–37 For example, we previously designed a human defensin-6 mimic peptide (HDMP), which recognizes S. aureus through BIF process from nanoparticles (NPs) to nanofibers (NFs) to capture S. aureus , inhibiting the invasion into host cells. 38…”