Construction and Piezoelectric Properties of a Single-Peptide Nanotube Composed of Cyclic β-peptides with Helical Peptides on the Side Chains

To develop nanopiezoelectronics, it is necessary to investigate the relationship between the sizes and piezoelectric properties of the material. Peptide nanotubes (PNTs) composed of cyclic β-peptides have been studied as leading candidates for nanopiezoelectric materials. The current drawback of PNTs is aggregation to form a PNT bundle structure due to strong dipole–dipole interactions between PNTs. Here, we report the construction and piezoelectric properties of single PNTs without nonspecific aggregation by side-chain modification of helical peptides. A cyclic tri-β-peptide with a helical peptide was prepared by multiple-step liquid-phase peptide synthesis and assembled into PNTs by the vapor diffusion method. These nanotubes were characterized by polarized light microscopy and Fourier transform infrared (FTIR) spectroscopy. Additionally, atomic force microscopy (AFM) topographic images showed nanotubes with a height of 4 nm, which corresponds to the diameter of a PNT on a gold-coated mica substrate, indicating that a single PNT was prepared successfully. The converted piezoelectric response of a single PNT was determined to be 1.39 ± 0.12 pm/V. This value was consistent with that of a PNT bundle, which reveals that the piezoelectricity of PNTs is induced by deformation of their cyclic skeletons and is independent of the bundled structure. This finding not only demonstrates a new molecular design strategy to construct these smallest piezoelectric biomaterials by controlling the supramolecular hierarchical structures but also provides insights into the correlation between molecular assembly morphology and size-dependent piezoelectric properties

Synthetic Mitochondria-Targeting Peptides Incorporating α-Aminoisobutyric Acid with a Stable Amphiphilic Helix Conformation in Plant Cells

In the genetic modification of plant cells, the mitochondrion is an important target in addition to the nucleus and plastid. However, gene delivery into the mitochondria of plant cells has yet to be established by conventional methods, such as particle bombardment, because of the small size and high mobility of mitochondria. To develop an efficient mitochondria-targeting signal (MTS) that functions in plant cells, we designed the artificial peptide (LURL)₃ and its analogues, which periodically feature hydrophobic α-aminoisobutyric acid (Aib, U) and cationic arginine (R), considering the consensus motif recognized by the mitochondrial import receptor Tom20. Circular dichroism measurements and molecular dynamics simulation studies revealed that (LURL)₃ had a propensity to form a stable α-helix in 0.1 M phosphate buffer solution containing 1.0 wt % sodium dodecyl sulfate. After internalization into plant cells via particle bombardment, (LURL)₃ revealed highly selective accumulation in the mitochondria, whereas its analogue (LARL)₃ was predominantly located in the vacuoles in addition to mitochondria. The high selectivity of (LURL)₃ can be attributed to the incorporation of Aib, which promotes the hydrophobic interaction between the MTS and Tom20 by increasing the hydrophobicity and helicity of (LURL)₃. The present study provided a prospective mitochondrial targeting system using the simple design of artificial peptides

Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect

BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT

A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): “Lactosome” Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy

“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific shortened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing feature. This review focuses on the combined advances in nanotechnology and material sciences utilizing the “89Zr-labeled CPP and TPP-loaded Lactosome particles” and future directions based on important milestones and recent developments in this platform

金表面上に自己集合したペプチドの電子特性と光電変換に関する研究

京都大学0048新制・課程博士博士(工学)甲第19898号工博第4214号新制||工||1651(附属図書館)32975京都大学大学院工学研究科材料化学専攻(主査)教授 木村 俊作, 教授 瀧川 敏算, 教授 今堀 博学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDGA

Chiral and random arrangements of flavin chromophores along cyclic peptide nanotubes on gold influencing differently on surface potential and piezoelectricity

Two kinds of peptide nanotubes are prepared from cyclo(β-Asp(flavin)-β-alanine-β-alanine) (C3FAA) and cyclo(β-Asp(flavin)-ethylenediamine-succinic acid) (C3FES). The flavin chromophores are protruding on the C3FAA and C3FES peptide nanotube surfaces in random and chiral ways, respectively. The surface potentials of the C3FAA nanotube bundles on a gold substrate become larger than the C3FES nanotube bundles of the corresponding thicknesses. The converse piezoelectric coefficients are as small as less than 1 pm V⁻¹. The peptide nanotube bundles are subjected to a thermal anneal treatment which raises up all the surface potentials and also the converse piezoelectricity of the C3FES nanotube bundles of 3 pm V⁻¹. The macrodipole of the C3FAA nanotube and the chiral arrangement of the flavin groups in the C3FES nanotube are considered to contribute influentially to the surface potential and the piezoelectricity, respectively

Engineering pH-responsive switching of donor–π–acceptor chromophore alignments along a peptide nanotube scaffold

A cyclic tri-β-peptide cyclo(β-Ala-β-Ala-β-Lys) having diethylaminonaphthalimide at the β-Lys side chain (CP3Npi) self-assembled into a peptide nanotube in a solution of HFIP and water. CD spectra of the CP3Npi nanotubes show a negative Cotton effect at 441 nm and a positive Cotton effect at 393 nm, indicating that D–π–A naphthalimide chromophores are aligned in a left-handed chiral way along the nanotube. The CP3Npi nanotubes bear positive charges under acidic conditions retaining the nanotube structure but pH-responsive switching of D–π–A naphthalimide alignments along the nanotube between a left-handed chiral and random arrangement was observed. The peptide nanotube is a stable scaffold for attaining pH-responsive alignment switching of side-chain chromophores

Joining Nanotubes Comprising Nucleobase-carrying Amphiphilic Polypeptides

Three kinds of amphiphilic polypeptides, X-poly(sarcosine)-b-(L-Leu-Aib)6 (X = adenine, thymine, glycolic acid), were synthesized and self-assembled in a tris buffer to take on nanotube morphology. The nanotubes were joined together to extend the nanotube length with the addition of trifluoroethanol and heat treatment at 50 °C for 24 h. The length extension rate decreased in the order of adenine > glycolic acid > thymine depending on the N-terminal chromophores. Adenine–adenine interactions between the nanotubes were found to be more prevalent upon joining the nanotubes than adenine–thymine interactions. Further, adenines on the nanotube surface could chelate with Cu(ii) to thermodynamically stabilize the nanotube membrane. AFM imaging in liquid environment revealed that the membrane elasticity of the adenine nanotube was as high as ca. 1 MPa, which is considered to be strengthened as a result of the adenine–adenine interactions

O₂‑Triggered Directional Switching of Photocurrent in Self-Assembled Monolayer Composed of Porphyrin- and Fullerene-Terminated Helical Peptides on Gold

Directional switching of photocurrent generation in response to oxygen is attained with the self-assembled monolayer (SAM) composed of porphyrin- and fullerene-terminated helical peptides. The anodic photocurrent of the porphyrin SAM under argon gas is successfully switched over to the cathodic photocurrent in the presence of oxygen gas only in the copresence of the fullerene-terminated helical peptide. The first-principle calculations explain that the cathodic photocurrent is promoted as a result of suppression of the anodic photocurrent due to the small electron coupling between the lowest unoccupied molecular orbitals of fullerene and the amide moieties of electron mediating helix peptides