Synthesis of All-Peptide-Based Rotaxane from a Proline-Containing Cyclic Peptide.

Rotaxane cross-linkers enhance the toughness of the resulting rotaxane cross-linked polymers through a stress dispersion effect, which is attributed to the mobility of the interlocked structure. To date, the compositional diversity of rotaxane cross-linkers has been limited, and the poor compatibility of these cross-linkers with peptides and proteins has made their use in such materials challenging. The synthesis of a rotaxane composed of peptides may result in a biodegradable cross-linker that is compatible with peptides and proteins, allowing the fortification of polypeptides and proteins and ultimately leading to the development of innovative materials that possess excellent mechanical properties and biodegradability.

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.

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.

A Novel Zr-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 Zr-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.

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) 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.

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.

A Novel Surface Modification and Immobilization Method of Anti-CD25 Antibody on Nonwoven Fabric Filter Removing Regulatory T Cells Selectively.

Anti-CD25 antibodies were immobilized on polypropylene (PP) nonwoven fabrics to specifically remove mouse regulatory T cells (Tregs) from mouse spleen cells. PP fibers were coated with peptide nanosheets, which were prepared by self-assembling of a mixture of X-poly(sarcosine)--(l-Leu-Aib) (X: glycolic acid or a phenylboronic acid) and Y-poly(sarcosine)--(d-Leu-Aib) (Y: glycolic acid or diazirine derivative). Anti-CD25 antibodies were immobilized by covalent linking between the sugar moiety of the antibody and the phenylboronic acid group on the peptide nanosheet.

Phase-Separated Molecular Assembly of a Nanotube Composed of Amphiphilic Polypeptides Having a Helical Hydrophobic Block.

Amphiphilic block polypeptides of poly(sarcosine)--(l- or d-Leu-Aib) (SL12OMe or SD12OMe) and poly(sarcosine)--(l-Leu-Aib) (SL14OMe) were reported to self-assemble into a nanotube morphology. Herein, we tried to construct a phase-separated nanotube by sticking two different kinds of nanotubes. SD12OMe nanotubes were found to stick to SL14OMe nanotubes with a heat treatment at 50 °C, but the sticking yield was limited.

Sterical Recognition at Helix-Helix Interface of Leu-Aib-Based Polypeptides with and without a GxxxG-Motif.

An amphiphilic polypeptide, poly(sarcosine)- b-(l-Leu-Aib) (SL16), was reported to self-assemble into vesicles. A GxxxG motif, which is known to induce helix dimerization, is incorporated into the hydrophobic helical block of SL16 to synthesize poly(sarcosine)- b-(l-Leu-Aib)-(Gly-Aib-l-Leu-Aib-Gly-Aib)-(l-Leu-Aib) (SG16). SG16 shows helix association in ethanol at a high concentration and low temperatures, which is not observed with SL16.

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.

Joining Nanotubes Comprising Nucleobase-carrying Amphiphilic Polypeptides.

Three kinds of amphiphilic polypeptides, X-poly(sarcosine)--(-Leu-Aib) (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 -terminal chromophores.

Piezoelectric property of bundled peptide nanotubes stapled by bis-cyclic-β-peptide.

Cyclic tetra-β-peptides (CP4s) and a bis-CP4 were synthesized to prepare peptide nanotubes (PNTs) by molecular stacking of cyclic peptides. The addition of bis-CP4 to the PNT preparation afforded PNT bundles increasing the direct and converse piezoelectiric coefficients, which is ascribable to bis-CP4 stapling PNTs into the parallel alignment of PNT dipoles.

Compartmentalized host spaces accommodating guest aromatic molecules in a chiral way in a helix-peptide-aromatic framework.

A novel host molecular assembly of a free-standing flat nanosheet with compartmentalized spaces was prepared using a bolaamphiphilic peptide composed of two amphiphilic helical peptides and an oligo(naphthaleneethynylene) (ONE) unit at the center of the molecule. The nanosheet possesses void host spaces that can accommodate two mol-equivalent ONE groups to form columns of ONE groups in a right-handed helical way and ONE channels over a long distance. The present molecular system therefore can provide a chiral pore channel for relatively large molecules.

Two one-dimensional arrays of naphthyl and anthryl groups along peptide nanotubes prepared from cyclic peptides comprising α- and β-amino acids.

A novel cyclic hexapeptide composed of l-α-naphthylalanine, d-α-anthrylalanine, and four β-alanines (CP6) is synthesized and its molecular assembly into peptide nanotubes (PNTs) and the electronic properties arising from one-dimensional arrays of aromatic groups along the PNTs were investigated. CP6 with a combination of l- and d-α-amino acids is designed to self-assemble into PNTs with them stacking on top of each other under the constraint of maximizing the number of intermolecular hydrogen bonds between the cyclic peptides. Upon PNT formation, the respective side chains of l- and d-α-amino acids are aligned in line along the PNTs.

Temperature-Induced Phase Separation in Molecular Assembly of Nanotubes Comprising Amphiphilic Polypeptoid with Poly( N-ethyl glycine) in Water by a Hydrophilic-Region-Driven-Type Mechanism.

Two kinds of amphiphilic polypeptoids having different types of hydrophilic polypeptoids, poly(sarcosine)- b-(l-Leu-Aib) (ML12) and poly( N-ethyl glycine)- b-(l-Leu-Aib) (EL12), were self-assembled via two paths to phase-separated nanotubes. One path was via sticking ML12 nanotubes with EL12 nanotubes and the other was a preparation from a mixture of ML12 and EL12 in solution. In either case, nanotubes showed temperature-induced phase separation along the long axis, which was observed by two methods of labeling one phase with gold nanoparticles and fluorescence resonance energy transfer between the components.

Effect of oscillation dynamics on long-range electron transfer in a helical peptide monolayer.

Electron transfer (ET) reactions via helical peptides composed of -(Aib-Pro)n- were studied in self-assembled monolayers and compared with -(Ala-Aib)n- peptides. Short Aib-Pro peptides showed slightly higher ET rates due to the better electronic coupling of the Pro residue. But, the 24mer Aib-Pro peptide showed a smaller ET rate than the corresponding Ala-Aib peptide.

Electronic properties of tetrathiafulvalene-modified cyclic-β-peptide nanotube.

Cyclic tri-β-peptide having tetrathiafulvalene (TTF) at the side chain was synthesized to prepare a peptide nanotube aligning TTF side chains along the nanotube. The polarized light microscopic observations revealed crystallization of the cyclic peptide by the vapor diffusion method. Fourier-transform infrared and electron diffraction measurements of the crystals clarified formation of homogeneous hydrogen bonds making a columnar structure with a layer spacing of 4.

Prevailing Photocurrent Generation of D-π-A Type Oligo(phenyleneethynylene) in Contact with Gold over Dexter-Type Energy-Transfer Quenching.

Photocurrent generation is observed with D-π-A type oligo(phenyleneethynylene) (OPE) physically contacting gold substrate. The OPE is conjugated with helical peptides, which helps the OPE moiety orient vertically on gold surface. This configuration makes the Dexter energy transfer difficult to occur even though one end of the D-π-A type OPE physically contacts gold.

Molecular direction dependence of single-molecule conductance of a helical peptide in molecular junction.

The helix-peptide dipole effect on single-molecule conductance was analysed experimentally and theoretically with a single 8mer helical peptide. The helical peptide was immobilized on a gold surface in two opposite directions of the helix dipole. Single-molecule conductance of the helical peptide was determined to be 2.

Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2.

Increase in bone resorption by osteoclasts can cause metabolic bone diseases, such as osteoporosis. Recent attention has been paid to the receptor activator of the NF-kappaB ligand (RANKL), an accelerator of osteoclast differentiation. RANKL is expressed on the bone marrow-derived stromal cell membrane and induces the differentiation of osteoclasts by binding to RANK expressed on the osteoclast precursor cell membrane.

Squalane as a possible carrier of bone morphogenetic protein.

Gelatin capsules containing squalane partially purified bone morphogenetic protein (BMP) complex were placed on the perimuscular membrane of rats. Two kinds of control, gelatin capsules containing only BMP and those bearing squalane only, were used. The embedded areas were histopathologically examined at 3 and 6 wk after the operation.

[Six cases of primary pulmonary cryptococcosis].

Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2.

[Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival].

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain.