Abstract
Creating thermally stable collagen mimetic peptides (CMPs) is a persistent challenge. Nature leverages covalent crosslinkings to stabilize collagen’s signature triple helical tertiary structure and higher-order assemblies. Herein, we demonstrate that crosslinkings between levodopa (Dopa) and lysine, amino acids present in native collagen, can covalently stabilize the triple helix in collagen mimetic peptides. Since alkaline conditions catalyze the oxidation of the catechol on Dopa to a benzoquinone, while being in proximity to the nucleophilic lysine, we hypothesized that this reaction could be a facile method to covalently capture the supramolecular structure of CMPs by simply increasing the pH of the aqueous solvent with the addition of sodium hydroxide. This covalent capture strategy successfully stabilizes CMP homotrimers and a de novo designed ABC-type heterotrimer demonstrating that the Lysine-Dopa covalent bond is best templated by a supramolecular, axial cation–π pairwise interaction. In nature, collagen can hierarchically assemble into fibers. This behavior can be mimicked with the self-assembly of CMPs, but the resulting nanofibers typically exhibit thermal stability below body temperature. In a final application, we demonstrate that Dopa–Lysine covalent capture also enhances the thermal stability of CMP nanofibers well above 37 °C. This biomimetic covalent capture strategy can stabilize a wide variety of CMP systems and potentially enable the biomedical application of these materials.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
† Supplementary Information available: Full peptide characterization including UPLC, MS data, CD melt curves; further covalent capture characterization data and hydrogel characterization. See DOI: 00.0000/00000000.
