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Molecular Engineering of the Peptoid Nanosheet Hydrophobic Core

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posted on 26.10.2016 by Ellen J. Robertson, Caroline Proulx, Jessica K. Su, Rita L. Garcia, Stan Yoo, Eric M. Nehls, Michael D. Connolly, Laudann Taravati, Ronald N. Zuckermann
The relationship between the structure of sequence-defined peptoid polymers and their ability to assemble into well-defined nanostructures is important to the creation of new bioinspired platforms with sophisticated functionality. Here, the hydrophobic N-(2-phenylethyl)­glycine (Npe) monomers of the standard nanosheet-forming peptoid sequence were modified in an effort to (1) produce nanosheets from relatively short peptoids, (2) inhibit the aggregation of peptoids in bulk solution, (3) increase nanosheet stability by promoting packing interactions within the hydrophobic core, and (4) produce nanosheets with a nonaromatic hydrophobic core. Fluorescence and optical microscopy of individual nanosheets reveal that certain modifications to the hydrophobic core were well tolerated, whereas others resulted in instability or aggregation or prevented assembly. Importantly, we demonstrate that substitution at the meta and para positions of the Npe aromatic ring are well tolerated, enabling significant opportunities to tune the functional properties of peptoid nanosheets. We also found that N-aryl glycine monomers inhibit nanosheet formation, whereas branched aliphatic monomers have the ability to form nanosheets. An analysis of the crystal structures of several N,N′-disubstituted diketopiperazines (DKPs), a simple model system, revealed that the preferred solid-state packing arrangement of the hydrophobic groups can directly inform the assembly of stable peptoid nanosheets.