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Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers.

ABSTRACT: Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofibers and demonstrate a remarkable physical stability even after attachment of poly(ethylene glycol). We employed small-angle neutron/X-ray scattering, circular dichroism spectroscopy, and molecular dynamics simulation techniques to investigate the detailed nanostructure, stability, and molecular exchange. The results for the most stable sequence did not reveal any structural alterations or unimer exchange for temperatures up to 85 °C in the biologically relevant pH range. Only under severe mechanical perturbation (i.e., tip sonication) would the fibers break up, which is reflected in a very high activation barrier for unimer exchange of ∼320 kJ/mol extracted from simulations. The results give important insight into the relation between molecular structure and stability of peptide nanostructure that is important for, e.g., biomedical applications.

SUBMITTER: Konig N

PROVIDER: S-EPMC10339792 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers.

König Nico N Szostak Szymon Mikolaj SM Nielsen Josefine Eilsø JE Dunbar Martha M Yang Su S Chen Weike W Benjamin Ari A Radulescu Aurel A Mahmoudi Najet N Willner Lutz L Keten Sinan S Dong He H Lund Reidar R

ACS nano 20230626 13

Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofi ...[more]

PMID: 37358231

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Project description:The majority of current vaccines depend on a continuous "cold chain" of storage and handling between 2 and 8°C. Vaccines experiencing temperature excursions outside this range can suffer from reduced potency. This thermal sensitivity results in significant losses of vaccine material each year and risks the administration of vaccines with diminished protective ability, issues that are heightened in the developing world. Here, using peptide self-assemblies based on the fibril-forming peptide Q11 and containing the epitopes OVA323-339 from ovalbumin or ESAT651-70 from Mycobacterium tuberculosis, the chemical, conformational, and immunological stability of supramolecular peptide materials were investigated. It was expected that these materials would exhibit advantageous thermal stability owing to their adjuvant-free and fully synthetic construction. Neither chemical nor conformational changes were observed for either peptide when stored at 45°C for 7days. ESAT651-70-Q11 was strongly immunogenic whether it was stored as a dry powder or as aqueous nanofibers, showing undiminished immunogenicity even when stored as long as six months at 45°C. This result was in contrast to ESAT651-70 conjugated to a protein carrier and adjuvanted with alum, which demonstrated marked thermal sensitivity in these conditions. Antibody titers and affinities were undiminished in mice for OVA323-339-Q11 if it was stored as assembled nanofibers, yet some diminishment was observed for material stored as a dry powder. The OVA study was done in a different mouse strain and with a different prime/boost regimen, and so it should not be compared directly with the study for the ESAT epitope. This work indicates that peptide self-assemblies can possess attractive thermal stability properties in the context of vaccine development.Statement of significanceAlmost all current vaccines must be maintained within a tight and refrigerated temperature range, usually between 2 and 8°C. This presents significant challenges for their distribution, especially in the developing world. Here we report on the surprisingly robust thermal stability of a self-assembled peptide vaccine. In particular a self-assembled peptide vaccine containing a tuberculosis epitope maintained all of its potency in mice when exposed to an extreme thermal treatment of six months at 45°C. In a different mouse model, we investigated another model epitope and found some storage conditions where potency was diminished. Overall this study illustrates that some self-assembled peptide vaccines can have remarkable thermal stability.

Dataset Information

Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers.

Publications

Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers.

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