DE, Soumen; CHI, Bo; GRANIER, Thierry; QI, Ting; MAURIZOT, Victor; HUC, Ivan

doi:10.1038/nchem.2854

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DE, Soumen
Institut Européen de Chimie et Biologie [IECB]

CHI, Bo
Institut Européen de Chimie et Biologie [IECB]

GRANIER, Thierry

Institut Européen de Chimie et Biologie [IECB]

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Nature Chemistry. 2018, vol. 10, n° 1, p. 51-57

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Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. 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. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that 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 with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.< Leer menos

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Protein folding

Self-assembly

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Designing cooperatively folded abiotic uni- and multimolecular helix bundles

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