β-Hairpin Fold Peptide Brush Polymers
- 1Northwestern University
Abstract
Peptide-brush polymers prepared via graft-through polymerization of peptide-based olefinic monomers form Protein-Like Polymers (PLPs) with demonstrated utility as chemical biology tools for modulating intracellular protein--protein interactions and are in development as a emerging class of therapeutic. This favorable bioactivity has been achieved in part by mimicking some of the structural and functional features of proteins, such as their dynamic, globular solution-phase structures, ability to insert into lipid membranes and enter cells, and tendency to enforce -helicity in peptide side chains. However, because structure leads to function, insight into the structure of these proteomimetic polymers, particularly their overall tertiary structure and the extent to which this influences the brush peptide structure, is incomplete. To further this understanding, we prepared a set of brush polymers incorporating the trpzip2 peptide sequence, commonly used as a model system for protein folding. We examine these polymers via circular dichroism spectroscopy, infrared spectroscopy, and small-angle X-ray scattering, coupled with insights from molecular dynamics simulations. Here, a loss of the {beta}-hairpin structure of the monomer is observed regardless of polymer composition, and simulations corroborate that the polymer backbone destabilizes local secondary structure, restricting peptide motion and altering the accessible free-energy landscape. This study provides insight into design rules governing these synthetic polymer-based proteomimetics.
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BibTeX
@misc{oktawiec2026βhairpin,
title = {{β-Hairpin Fold Peptide Brush Polymers}},
author = {J. Oktawiec and H. Nadeem and O. Ebrahim and Y. Chen and C. Barbut and J. Byrnes and M. Thompson and D. Shukla and N. Gianneschi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756272},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756272v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - β-Hairpin Fold Peptide Brush Polymers
AU - J. Oktawiec
AU - H. Nadeem
AU - O. Ebrahim
AU - Y. Chen
AU - C. Barbut
AU - J. Byrnes
AU - M. Thompson
AU - D. Shukla
AU - N. Gianneschi
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756272
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756272v1
AB - Peptide-brush polymers prepared via graft-through polymerization of peptide-based olefinic monomers form Protein-Like Polymers (PLPs) with demonstrated utility as chemical biology tools for modulating intracellular protein--protein interactions and are in development as a emerging class of therapeutic. This favorable bioactivity has been achieved in part by mimicking some of the structural and functional features of proteins, such as their dynamic, globular solution-phase structures, ability to insert into lipid membranes and enter cells, and tendency to enforce -helicity in peptide side chains. However, because structure leads to function, insight into the structure of these proteomimetic polymers, particularly their overall tertiary structure and the extent to which this influences the brush peptide structure, is incomplete. To further this understanding, we prepared a set of brush polymers incorporating the trpzip2 peptide sequence, commonly used as a model system for protein folding. We examine these polymers via circular dichroism spectroscopy, infrared spectroscopy, and small-angle X-ray scattering, coupled with insights from molecular dynamics simulations. Here, a loss of the {beta}-hairpin structure of the monomer is observed regardless of polymer composition, and simulations corroborate that the polymer backbone destabilizes local secondary structure, restricting peptide motion and altering the accessible free-energy landscape. This study provides insight into design rules governing these synthetic polymer-based proteomimetics.
ER -