Designing cooperatively folded abiotic uni- and multimolecular helix bundles

International audienceAbiotic foldamers, i.e. foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different from those of peptides and nucleotides, just like peptides and nucleotides differ from each. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix-bundles. Computations allowed to introduce hydrogen bonding functionalities at defined locations on aromatic amide backbones that eventually promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles having structures distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted upon subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behavior