Peptides as New Smart Bionanomaterials: Molecular‐Recognition and Self‐Assembly Capabilities

Biomolecules express exquisite properties that are required for molecular recognition and self‐assembly on the nanoscale. These smart capabilities have developed through evolution and such biomolecules operate based on smart functions in natural systems. Recently, these remarkable smart capabilities have been utilized in not only biologically related fields, but also in materials science and engineering. A peptide‐screening technology that uses phage‐display systems has been developed based on this natural smart evolution for the generation of new functional peptide bionanomaterials. We focused on peptides that specifically bound to synthetic polymers. These polymer‐binding peptides were screened by using a phage‐display peptide library to recognize nanostructures that were derived from polymeric structural features and were utilized for possible applications as new bionanomaterials. We also focused on self‐assembling peptides with β‐sheet structures that formed nanoscale, fibrous structures for applications in new bottom‐up nanomaterials. Moreover, nanofiber‐binding peptides were also screened to introduce the desired functionalities into nanofibers without the need for additional molecular design. Our approach to construct new bionanomaterials that employ peptides will open up excellent opportunities for the next generation of materials science and technology.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules V. Release properties of ethylcellulose layered matrix granules

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. In previous papers, a combination of the square-root time law and cube-root law equations was confirmed to be a useful equation for qualitative treatment. It was also confirmed that the combination equation could analyze the release properties of layered granules as well as matrix granules. The drug release property from layered granules is different from that of matrix granules. A time lag occurs before release, and the entire release property of layered granules was analyzed using the combination of the square-root time law and cube-root law equations. It is considered that the analysis method is very useful and efficient for both matrix and layered granules. Comparing the granulation methods, it is easier to control the manufacturing process by tumbling granulation (method B) than by tumbling-fluidized bed granulation (method C). Ethylcellulose (EC) layered granulation by a fluidized bed granulator might be convenient for the preparation of controlled release dosage forms as compared with a tumbling granulator, because the layered granules prepared by the fluidized bed granulator can granulate and dry at the same time. The time required for drying by the fluidized bed granulator is shorter than that by the tumbling granulator, so the fluidized bed granulator is convenient for preparation of granules in handling and shorter processing time than the tumbling granulator. It was also suggested that the EC layered granules prepared by the fluidized bed granulator were suitable for a controlled release system as well as the EC matrix granules.     

Design of peptides that form amyloid-like fibrils capturing amyloid beta1-42 peptides

Amyloid beta-peptide (Abeta) plays a critical role in Alzheimer's disease (AD). The monomeric state of Abeta can self-assemble into oligomers, protofibrils, and amyloid fibrils. Since the fibrils and soluble oligomers are believed to be responsible for AD, the construction of molecules capable of capturing these species could prove valuable as a means of detecting these potentially toxic species and of providing information pertinent for designing drugs effective against AD. To this aim, we have designed short peptides with various hydrophobicities based on the sequence of Abeta14-23, which is a critical region for amyloid fibril formation. The binding of the designed peptides to Abeta and the amplification of the formation of peptide amyloid-like fibrils coassembled with Abeta are elucidated. A fluorescence assay utilizing thioflavin T, known to bind specifically to amyloid fibrils, revealed that two designed peptides (LF and VF, with the leucine and valine residues, respectively, in the hydrophobic core region) could form amyloid-like fibrils effectively by using mature Abeta1-42 fibrils as nuclei. Peptide LF also coassembled with soluble Abeta oligomers into peptide fibrils. Various analyses, including immunostaining with gold nanoparticles, enzyme-linked immunosorbent assays, and size-exclusion chromatography, confirmed that the LF and VF peptides formed amyloid-like fibrils by capturing and incorporating Abeta1-42 aggregates into their peptide fibrils. In this system, small amounts of mature Abeta1-42 fibrils or soluble oligomers could be transformed into peptide fibrils and detected by amplifying the amyloid-like fibrils with the designed peptides.     

Phosphate-mediated molecular memory driven by two different protein kinases as information input elements

There is increasing interest in studying molecular-based devices that perform Boolean logic operations whose output state (0 or 1) depends on the input conditions (0/0, 1/0, 0/1, or 1/1). So far, great efforts have been devoted to establish molecular-scaled logic gates activated by chemical, physical, and biological inputs. We herein describe the design and synthesis of a tandem protein kinase substrate peptide acting as a phosphate-mediated molecular memory. The molecular-based memory system is comprised of two different phosphorylatable substrate regions joined in series and a spiropyran derivative at the N-terminus. We also demonstrated three basic "AND", "OR", and "NOR" logic operations on the basis of alterations in the spiropyran-to-merocyanine (SP-to-MC) thermocoloration properties of the spiropyran moiety in the peptide upon kinase-catalyzed phosphorylation. The three logic functions were successfully performed by adding ionic polymers as programming elements with preset thresholds of a signal intensity in a microplate format. Throughout this study, information was recorded on the substrate peptide by protein kinase-catalyzed phosphorylation, stored stably as phosphoesters, read according to the extent of the SP-to-MC thermocoloration, and erased by phosphatase-catalyzed dephosphorylation, resulting in the peptide returning to the initial recordable state. Thus, the proof-of-concept experiments described herein could be used to provide clues for developing practical molecular-based processing and computing.     

Surface structures of rutile TiO2 (011)

Surface structures of rutile TiO(2) (011) are determined by a combination of noncontact atomic force microscopy (NC-AFM), scanning tunneling microscopy (STM), and density functional calculations. The surface exhibits rowlike (n x 1) structures running along the [01] direction. Microfaceting missing-row structural models can explain the experimental results very well. Calculated images for NC-AFM and STM are in good agreement with the experimental results. A decrease of the density of dangling bonds stabilizes the surface energy, which results in the microfaceting missing-row reconstructions.     

A hetero-core structured fiber optic pH sensor

Novel spectroscopic sensor based on a hetero-core structured fiber optic is described in this paper. The hetero-core structured fiber optic consists of multi mode fibers and a short piece of single mode fiber which was inserted in the multi mode fibers. Phenol red and/or cresol red as pH sensitive dyes were immobilized on the surface of the hetero-core portion by using sol-gel method, and the pH change detection was performed by immersing the hetero-core portion into the solution. In the case that the cresol-red immobilized fiber was immersed in the alkaline and/or acidic solution, the peak wavelength of the propagating loss spectra were about 575 and 545 nm, respectively. These propagating loss spectra were similar to that of the absorbance spectra of the dye solution. In the propagating loss spectra of phenol-red immobilized fiber, these spectra were similar to that of the dye solution. The colorimetric change of the dye in the support matrix was reversible, and the response time of the sensor was within 30 s.     

Atomic structures of the defective SrTiO3 (001) surface

Surface structures of defective SrTiO(3) (001) have been studied by using scanning probe microscopy and density functional theory calculations. We observed several defective surface structures with true atomic resolution under reducing ultrahigh vacuum conditions. It is found that all the defects are terminated by (001), (100) and (010) microfacets of the TiO(2) plane. We propose microfaceting TiO(2) termination with Sr adatom models. The formation of various types of defects is driven by the changes of the surface stoichiometry depending on surface preparations.     

Preparation and evaluation of combination tablet containing incompatible active ingredients

Combination preparation plays an important role in clinical treatment because of its better and wider curative synergism and weaker side effects. However, the existence of incompatibility between active ingredients or between active ingredients and excipients presents a serious obstacle in the preparation of such combination solid dosage forms. In this study, aspirin and ranitidine hydrochloride, between which there existed a chemical interaction, were selected as model drugs. Aspirin powders without any additives were granulated with hydroxypropyl methyl cellulose (HPMC) water solution as a binder using a Wurster coating apparatus and the operation conditions were optimized by Artificial Neural Network (ANN) analysis. Under these conditions, the aspirin granules prepared showed good flowability and compressibility. On the other hand, ranitidine hydrochloride was coated with Aquacoat (ethyl cellulose aqueous dispersion) after preliminary granulation with the Wurster coating apparatus. The aspirin granules and coated ranitidine hydrochloride particles were compressed into tablets with suitable excipients. The combination tablets showed good dissolution, content uniformity and improved stability of active ingredients.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules II. effects of the binder solution on the release process

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC) matrix granules prepared by an extrusion granulation method were examined. The release process could be divided into two parts; the first and second stages were analyzed by applying square-root time law and cube-root law equations, respectively. The validity of the treatments was confirmed by the fitness of a simulation curve with the measured curve. In the first stage, PPA was released from the gel layer of swollen EC in the matrix granules. In the second stage, the drug existing below the gel layer dissolved and was released through the gel layer. The effect of the binder solution on the release from EC matrix granules was also examined. The binder solutions were prepared from various EC and ethanol (EtOH) concentrations. The media changed from a good solvent to a poor solvent with decreasing EtOH concentration. The matrix structure changed from loose to compact with increasing EC concentration. The preferable EtOH concentration region was observed when the release process was easily predictable. The time and release ratio at the connection point of the simulation curves were also examined to determine the validity of the analysis.     

Construction of a protein-detection system using a loop peptide library with a fluorescence label

Construction of a novel protein-detection system was carried out using a designed peptide library with fluorescent labels based on loop structures. As a basic model study, detection of alpha-amylase using fluorescent-labeled peptides derived from an active loop of tendamistat was examined. The detection methods for proteins with immobilized peptides as well as peptides in solution have been successfully established. Based on these results, a loop peptide library that has various turn sequences grafted on a stable loop structure has been constructed. Various proteins with recognition patterns corresponding, for instance, to "protein fingerprints" could be detected using an immobilized peptide library. The present results suggest that the system can be applied to the development of a peptide microarray that behaves as a protein chip.