Amphiphilic diblock polypeptoids were synthesized with the same hydrophilic block but the different hydrophobic block which comprised phenylethyl side chains with bromine atoms appended to meta or para position. Crystalline polypeptoid nanosheets formed by self-assembly of polypeptoid molecules in water were imaged using cryogenic electron microscopy (Cryo-EM). Low-dose cryogenic electron microscopy micrographs were obtained from frozen hydrated crystalline nanosheets. A hybrid processing of crystallographic, tomography and single particle methods, developed for cryo-electron microscopy of biological macromolecules, was used to resolve the structure of crystals with atomic resolution in three dimensions. Interestingly, the V-shaped motif, which is the projection of individual polypeptoid molecule from the top view of the nanosheet, is packed in different orientation (parallel vs. antiparallel) depending on the position of bromine atom in the phenylethyl side chains. Nanosheets comprising phenylethyl side chains with bromine atoms appended to meta position showed parallel V-shaped motifs while nanosheets comprising phenylethyl side chains with bromine atoms appended to para position exhibited antiparallel V-shaped motif. Our approach is robust and enable direct three-dimensional visualization of the arrangement of polypeptoid backbones and side chains in crystalline nanosheets. It reveals the effect of side chain chemistry on the crystalline structure of polypeptoid nanosheets at the atomic level.

Cryo-EM reveals the effect of side chain chemistry on the crystalline structures of polypeptoid nanosheets

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.