Peptide\nBundlemer Networks or Lattices: Controlling\nCross-Linking and Self-Assembly Using Protein-like Display of Chemistry

Coiled-coil ‘bundlemer’\npeptides were selectively\nmodified with allyloxycarbonyl (alloc)-protected lysine, a non-natural\namino acid containing an alkene on its side chain. The specific display\nof this alkene from the coiled-coil surface with protein-like specificity\nenabled this residue to be used as a covalent linkage for creating\npeptide networks with controllable properties or as a physical linkage\nfor the self-assembly of bundlemers into unexpected, intricate lattices\ndriven by the hydrophobic nature of the side chain. For network formation,\npeptides were modified with both alloc-protected lysine and cysteine\namino acids for solution assembly into solvent-swollen films and subsequent\ncovalent cross-linking via thiol–ene photo click reactions.\nThe degree of network cross-linking, as determined by rheometry, was\nfinely tuned by varying the specific spatial display of reactive groups\non the bundlemer building block particles, transitioning between intrabundle\nand interbundle cross-linking. The designed display of alloc groups\nfrom the center of the bundlemer building block also prompted particle\nself-assembly into an unexpected intricate lattice with a porous morphology.\nThe lattices were studied in a variety of solution conditions using\ntransmission electron microscopy, cryotransmission electron microscopy,\nand small-angle X-ray scattering. The approximate particle arrangement\nin the lattice was determined by using coarse-grained modeling and\nmachine learning optimization techniques along with experimental methods.\nThe proposed truss-like face-centered cubic packing of the alloc-functionalized\nbundlemers agrees well with the experimental results.