biostudies-literatureYu SLeona M. and Harry B. Helmsley Charitable TrustAmerican Diabetes Association Research FoundationJDRFNIGMS NIH HHSe2311498https://www.ebi.ac.uk/biostudies/studies/S-EPMC11031314biostudies-literatureUnknown36(16)Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular β-sheet formation underlying 1D fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue. Here, a peptide bearing a prosthetic glucose-binding phenylboronic acid (PBA) is demonstrated to self-assemble into an uncommon nanocoil morphology. These nanocoils arise from antiparallel β-sheets, with molecules aligned parallel to the long axis of the coil. The binding of glucose to the PBA motif stabilizes and elongates the nanocoil, driving entanglement and gelation at physiological glucose levels. The glucose-dependent gelation of these materials is then explored for the encapsulation and release of a therapeutic agent, glucagon, that corrects low blood glucose levels. Accordingly, the release of glucagon from the nanocoil hydrogels is inversely related to glucose level. When evaluated in a mouse model of severe acute hypoglycemia, glucagon delivered from glucose-stabilized nanocoil hydrogels demonstrates increased protection compared to delivery of the agent alone or within a control nanocoil hydrogel that is not stabilized by glucose.Advanced materials (Deerfield Beach, Fla.)Glucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs.PMC110313142019PG‐T1D016R35 GM1225105‐CDA‐2020‐947‐A‐NR35 GM1379871‐19‐ACE‐312102‐04994Yu SEgelman EHPramudya IFlores BXian SYe ZSonani RRNativ-Roth ERoy RXiang YWebber MJBitton RLiu GfalseGlucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs.Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular β-sheet formation underlying 1D fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue. Here, a peptide bearing a prosthetic glucose-binding phenylboronic acid (PBA) is demonstrated to self-assemble into an uncommon nanocoil morphology. These nanocoils arise from antiparallel β-sheets, with molecules aligned parallel to the long axis of the coil. The binding of glucose to the PBA motif stabilizes and elongates the nanocoil, driving entanglement and gelation at physiological glucose levels. The glucose-dependent gelation of these materials is then explored for the encapsulation and release of a therapeutic agent, glucagon, that corrects low blood glucose levels. Accordingly, the release of glucagon from the nanocoil hydrogels is inversely related to glucose level. When evaluated in a mouse model of severe acute hypoglycemia, glucagon delivered from glucose-stabilized nanocoil hydrogels demonstrates increased protection compared to delivery of the agent alone or within a control nanocoil hydrogel that is not stabilized by glucose.2024-01-01T00:00:00Z2024 Apr2025-07-02T03:04:27.881Z2025-07-02T03:04:27.881ZS-EPMC110313143809590410.1002/adma.202311498