Controlling Amphiphilic Polymer Folding beyond the Primary Structure with Protein-Mimetic Di(Phenylalanine)

Warren, Jacqueline L.; Dykeman-Bermingham, Peter A.; Knight, Abigail S.

doi:10.1021/jacs.1c05659

Title: Controlling Amphiphilic Polymer Folding beyond the Primary Structure with Protein-Mimetic Di(Phenylalanine)

Journal Article · 10 August 2021 · Journal of the American Chemical Society

DOI: https://doi.org/10.1021/jacs.1c05659 · OSTI ID:1865831

Warren, Jacqueline L. ^[1]; Dykeman-Bermingham, Peter A. ^[2];

^[2]

Univ. of North Carolina, Chapel Hill, NC (United States); University of North Carolina, Chapel Hill
Univ. of North Carolina, Chapel Hill, NC (United States)

While methods for polymer synthesis have proliferated, their functionality pales in comparison to natural biopolymers–strategies are limited for building the intricate network of noncovalent interactions necessary to elicit complex, protein-like functions. Using a bioinspired di(phenylalanine) acrylamide (FF) monomer, we explored the impact of various noncovalent interactions in generating ordered assembled structures. In this work, amphiphilic copolymers were synthesized that exhibit β-sheet-like local structure upon collapsing into single-chain assemblies in aqueous environments. Systematic analysis of a series of amphiphilic copolymers illustrated that the global collapse is primarily driven by hydrophobic forces. Hydrogen-bonding and aromatic interactions stabilize local structure, as β-sheet-like interactions were identified via circular dichroism and thioflavin T fluorescence. Similar analysis of phenylalanine (F) and alanine-phenylalanine acrylamide (AF) copolymers found that distancing the aromatic residue from the polymer backbone is sufficient to induce β-sheet-like local structure akin to the FF copolymers; however, the interactions between AF subunits are less stable than those formed by FF. Further, hydrogen-bond donating hydrophilic monomers disrupt internal structure formed by FF within collapsed assemblies. Collectively, these results illuminate design principles for the facile incorporation of multiple facets of protein-mimetic, higher-order structure within folded synthetic polymers.

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Research Organization:: Univ. of North Carolina, Chapel Hill, NC (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Cancer Institute (NCI); National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: SC0021295

OSTI ID:: 1865831

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 33 Vol. 143; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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