Bioorthogonal Polymerization of Coiled-Coil Peptides

10 May 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Peptides capable of forming homotetrameric coiled-coil bundles are utilized as the monomeric building blocks (“bundlemers”) to synthesize hybrid polymers consisting of covalently linked coiled-coil microdomains with regularly spaced ethylene glycol repeats via tetrazine ligation with trans-cyclooctene. We confirm the formation of long, semiflexible rods with a Kuhn length of 6 - 7 nm and a molecular weight of 100 - 3,000 kDa. Polymerization at tetrazine concentrations > 5 mM results in the formation of mechanically robust hydrogels with defined viscoelastic properties through chain entanglements. Copolymerization of coiled-coil peptides with distinct composition and thermal stability gives rise to hydrogels that are thermally tractable. Solid-to-fluid transition occurs when one of the coiled-coil repeats melts. Upon cooling, solid-like properties are partially recovered through intermolecular association of the helical peptides. Overall, tetrazine ligation has enabled the covalent polymerization of self-assembled coiled-coil motifs for the establishment of protein-like linear polymers with unprecedent molecular weight.


tetrazine ligation
coiled-coil peptides
semiflexible rod

Supplementary materials

Video showing hydrogel formation during bioorthogonal polymerization of coiled coil peptides


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