ABSTRACT
Synthetic polypeptides have received increasing attention due to their ability to form higher ordered structures similar to proteins. The control over their secondary structures, which enables dynamic conformational changes, is primarily accomplished by tuning the side-chain hydrophobic or ionic interactions. Herein we report a strategy to modulate the conformation of polypeptides utilizing donor-acceptor interactions emanating from side-chain H-bonding ligands. Specifically, 1,2,3-triazole groups, when incorporated onto polypeptide side-chains, serve as both H-bond donors and acceptors at neutral pH and disrupt the α-helical conformation. When protonated, the resulting 1,2,3-triazolium ions lose the ability to act as H-bond acceptors, and the polypeptides regain their α-helical structure. The conformational change of triazole polypeptides in response to the donor-acceptor pattern was conclusively demonstrated using both experimental-based and simulation-based methods. We further showed the utility of this transition by designing smart, cell-penetrating polymers that undergo acid-activated endosomal escape in living cells.Hydrogen bonding plays a major role in determining the tridimensional structure of biopolymers. Here, the authors show that control over a polypeptide conformation can be achieved by altering the donor-acceptor properties of side-chain triazole units via protonation-deprotonation.
Subject(s)
Hydrogen Bonding , Ligands , Peptides/metabolism , Protein Conformation, alpha-Helical , Protein Structure, Secondary , Animals , Biopolymers , HeLa Cells , Humans , Hydrogen-Ion Concentration , Mice , Microscopy, Confocal , Models, Molecular , NIH 3T3 Cells , Protein Conformation , Spectrum Analysis , Triazoles/metabolismABSTRACT
Surfactant-resistant polymersomes have substantial potential to be used as delivery vehicles in industrial applications. Herein, we report the preparation of poly(ethylene oxide)-block-polystyrene copolymers with ultrahigh hydrophobic-block molecular weights through RAFT dispersion polymerization, which allows the polymerization-induced self-assembly into well-defined polymersomes with ultrathick membranes up to â¼47 nm. These ultrathick membranes significantly enhance the resistance against surfactant solubilization of the vesicles, improving the vesicles' potential for use in industrial encapsulations. Vesicle-encapsulated actives are well retained in the presence of up to 40 wt % of various anionic and nonionic surfactants, with less than 7% active leakage being observed after 30 days.