Rod-like architecture and cross-sectional structure of an amyloid protofilament-like peptide supermolecule in aqueous solution

Minami, Takuma; Matsumoto, Sakiko; Sanada, Yusuke; Waku, Tsuyoshi; Tanaka, Naoki; Sakurai, Kazuo

doi:10.1038/pj.2015.97

Cited by 4 publications

(10 citation statements)

References 20 publications

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“…In the present study, the electrostatically neutral αAC nanofibers were prepared by optimizing the mixing ratio of the anionic αAC(71-88) peptides and the cationic variants αAC(71-88)Antp peptides ( Fig 1C; S4 Fig in S1 File). Fig 1A shows proposed structures of the neutral peptide nanofibers, estimated on the basis of our previous studies [43,44].…”

Section: Discussionmentioning

confidence: 99%

Development of a brain-permeable peptide nanofiber that prevents aggregation of Alzheimer pathogenic proteins

et al. 2020

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Alzheimer's disease (AD) is proposed to be induced by abnormal aggregation of amyloidβ in the brain. Here, we designed a brain-permeable peptide nanofiber drug from a fragment of heat shock protein to suppress aggregation of the pathogenic proteins. To facilitate delivery of the nanofiber into the brain, a protein transduction domain from Drosophila Antennapedia was incorporated into the peptide sequence. The resulting nanofiber efficiently suppressed the cytotoxicity of amyloid βby trapping amyloid β onto its hydrophobic nanofiber surface. Moreover, the intravenously or intranasally injected nanofiber was delivered into the mouse brain, and improved the cognitive function of an Alzheimer transgenic mouse model. These results demonstrate the potential therapeutic utility of nanofibers for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Development of a brain-permeable peptide nanofiber that prevents aggregation of Alzheimer pathogenic proteins

et al. 2020

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“…In addition, structural analysis by small‐angle X‐ray scattering showed that the cross‐section of the nanofibers was rectangular and not circular, so it is unlikely they were cylindrical micelles, presumably because of the laminated structure of the β‐sheets (Fig. (c)) . We are now investigating both the interaction of the nanofibers with cells and the efficiency of the immune response induction by the nanofibers in vivo .…”

Section: β‐Sheet Fibrous Nano‐assembly For Drug Delivery System Applimentioning

confidence: 99%

“…Our group has also studied peptide nanofibers for cancer vaccine delivery; they were prepared by using self‐assembly of building blocks containing antigenic peptides . We focused on a β‐sheet‐based fibrous assembly as the driving force for the preparation of antigen‐loaded nano‐assemblies (Fig.…”

Section: β‐Sheet Fibrous Nano‐assembly For Drug Delivery System Applimentioning

confidence: 99%

Recent advances in nanofibrous assemblies based on β‐sheet‐forming peptides for biomedical applications

Waku

Tanaka

2016

Polymer International

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Amyloid fibrils are supramolecular polymers with -sheet-rich structures formed by polymerization of protein/peptide with intermolecular interaction. Amyloid fibrils have been miscast as toxic villains since they have historically been studied as pathogens associated with serious diseases, including Alzheimer's and Parkinson's disease. However, recent studies on their toxicity and formation mechanism and discovery of their functionality in nature correct the misconception and strongly facilitate the possible use of -sheet-forming peptides in designing novel nanomaterials. Self-assembly based on -sheet-forming peptides can provide highly ordered nanostructures under certain conditions. Therefore, ingenious design of the building block peptides allows the construction of nano-assemblies, which contain large quantities of bio-functional molecules, including drugs and bioactive peptides, and exhibit unique properties, such as assembly or disassembly in response to external stimulus or specific molecules. These properties provide a novel strategy for the creation of innovative nanomaterials, especially for biomedical applications. Here, we describe recent progress in the biomedical application of fibrous assemblies based on -sheet-forming peptides, such as the suppression of aberrant protein aggregation, controlled release, tissue engineering and other applications. This review focuses not only on the function of the nanofibrous assemblies but also on the functions of component molecules, namely amyloidogenic peptides.

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“…In previous work, we reported the preparation of antigen-loaded NFs by exploiting the self-assembly of β-sheet peptides [33,34] conjugated to antigenic peptides and hydrophilic chains, such as oligo-ethylene glycol (EG) [35,36,37]. MHC class I restricted epitope (SIINFEKL) from ovalbumin was selected as a model antigenic peptide.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, structural analysis revealed that the shape of the NFs is rectangular, rather than a cylinder-like structure observed for filament micelles, possibly because of the lamination structures of β-sheets. Based on this finding, the structural model was proposed as shown in Figure 1b, which shows that the surface of the NFs is not covered with EG chains homogeneously [35,36]. Thus, we hypothesized that the EG chain length is an important parameter for tuning the cellular interactions of NFs, including cellular uptake, cytotoxicity, and immune stimulation response.…”

Section: Introductionmentioning

confidence: 99%

Effect of the Hydrophilic-Hydrophobic Balance of Antigen-Loaded Peptide Nanofibers on Their Cellular Uptake, Cellular Toxicity, and Immune Stimulatory Properties

Waku

Nishigaki

Kitagawa

et al. 2019

IJMS

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Recently, nanofibers (NFs) formed from antigenic peptides conjugated to β-sheet-forming peptides have attracted much attention as a new generation of vaccines. However, studies describing how the hydrophilic-hydrophobic balance of NF components affects cellular interactions of NFs are limited. In this report, three different NFs were prepared by self-assembly of β-sheet-forming peptides conjugated with model antigenic peptides (SIINFEKL) from ovalbumin and hydrophilic oligo-ethylene glycol (EG) of differing chain lengths (6-, 12- and 24-mer) to investigate the effect of EG length of antigen-loaded NFs on their cellular uptake, cytotoxicity, and dendritic cell (DC)-stimulation ability. We used an immortal DC line, termed JAWS II, derived from bone marrow-derived DCs of a C57BL/6 p53-knockout mouse. The uptake of NFs, consisting of the EG 12-mer by DCs, was the most effective and activated DC without exhibiting significant cytotoxicity. Increasing the EG chain length significantly reduced cellular entry and DC activation by NFs. Conversely, shortening the EG chain enhanced DC activation but increased toxicity and impaired water-dispersibility, resulting in low cellular uptake. These results show that the interaction of antigen-loaded NFs with cells can be tuned by the EG length, which provides useful design guidelines for the development of effective NF-based vaccines.

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Rod-like architecture and cross-sectional structure of an amyloid protofilament-like peptide supermolecule in aqueous solution

Cited by 4 publications

References 20 publications

Development of a brain-permeable peptide nanofiber that prevents aggregation of Alzheimer pathogenic proteins

Development of a brain-permeable peptide nanofiber that prevents aggregation of Alzheimer pathogenic proteins

Recent advances in nanofibrous assemblies based on β‐sheet‐forming peptides for biomedical applications

Effect of the Hydrophilic-Hydrophobic Balance of Antigen-Loaded Peptide Nanofibers on Their Cellular Uptake, Cellular Toxicity, and Immune Stimulatory Properties

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