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Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels

Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic pepti...

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Autores principales: Agrahari, Ashutosh, Lipton, Mark, Chmielewski, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574645/
https://www.ncbi.nlm.nih.gov/pubmed/37836285
http://dx.doi.org/10.3390/nano13192645
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author Agrahari, Ashutosh
Lipton, Mark
Chmielewski, Jean
author_facet Agrahari, Ashutosh
Lipton, Mark
Chmielewski, Jean
author_sort Agrahari, Ashutosh
collection PubMed
description Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic peptide helix. The major product of the disulfide-stapling reaction was found to be composed of five amphiphilic peptides, thereby going from a 16-amino-acid peptide to a stapled 80-residue protein in one step. The structure of this pentamer, 5HB1, was optimized in silico, indicating a significant hydrophobic cavity of ~6 Å within a helical barrel. Metal-ion-promoted assembly of the helical barrel building blocks generated higher order assemblies with a three-dimensional (3D) matrix morphology. The matrix was decorated with hydrophobic dyes and His-tagged proteins both before and after assembly, taking advantage of the hydrophobic pocket within the helical barrels and coordination sites within the metal ion-peptide framework. As such, this peptide-based biomaterial has potential for a number of biotechnology applications, including supplying small molecule and protein growth factors during cell and tissue growth within the matrix.
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spelling pubmed-105746452023-10-14 Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels Agrahari, Ashutosh Lipton, Mark Chmielewski, Jean Nanomaterials (Basel) Article Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic peptide helix. The major product of the disulfide-stapling reaction was found to be composed of five amphiphilic peptides, thereby going from a 16-amino-acid peptide to a stapled 80-residue protein in one step. The structure of this pentamer, 5HB1, was optimized in silico, indicating a significant hydrophobic cavity of ~6 Å within a helical barrel. Metal-ion-promoted assembly of the helical barrel building blocks generated higher order assemblies with a three-dimensional (3D) matrix morphology. The matrix was decorated with hydrophobic dyes and His-tagged proteins both before and after assembly, taking advantage of the hydrophobic pocket within the helical barrels and coordination sites within the metal ion-peptide framework. As such, this peptide-based biomaterial has potential for a number of biotechnology applications, including supplying small molecule and protein growth factors during cell and tissue growth within the matrix. MDPI 2023-09-26 /pmc/articles/PMC10574645/ /pubmed/37836285 http://dx.doi.org/10.3390/nano13192645 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agrahari, Ashutosh
Lipton, Mark
Chmielewski, Jean
Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title_full Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title_fullStr Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title_full_unstemmed Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title_short Metal-Promoted Higher-Order Assembly of Disulfide-Stapled Helical Barrels
title_sort metal-promoted higher-order assembly of disulfide-stapled helical barrels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574645/
https://www.ncbi.nlm.nih.gov/pubmed/37836285
http://dx.doi.org/10.3390/nano13192645
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