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Tomoyuki Morita

Publications and source records attributed to Tomoyuki Morita.

At least 19 recordsLinked to original sources
PubMed2006

Helix triangle: unique peptide-based molecular architecture.

We here report a unique cyclic peptide structure, "helix triangle", as a unique example of peptide-based molecular architecture. The cyclic peptide is designed to have a triangular shape in which three 9mer helical peptide units make the sides and three pyrene derivatives make the apexes. The helical peptide units are ideally linear, and the pyrene units are ideal 60 degrees angular components. The yield of the cyclic peptide was relatively high despite its large cycle size. Absorption and fluorescence spectroscopy revealed that the three pyrene units do not interact with each other electronically, and circular dichroism spectroscopy indicated that the helical peptide units take 3(10)-helical conformation. Geometry optimization by the semi-empirical molecular orbital method gave a triangular structure with 3(10)-helices as the plausible molecular structure. To gain more information on the geometry and demonstrate one example of its self-assemblies, the monolayer of the cyclic peptide was prepared at the air/water interface, and its surface pressure-molecular area isotherm was studied. The isotherm indicated formation of a stable monolayer and suggested that the cyclic peptide actually takes the triangular structure predicted by the geometry optimization. The monolayer was then transferred onto a substrate and characterized by various methods. Ellipsometry and infrared reflection-absorption spectroscopy confirmed that the cyclic peptide has horizontal orientation to the surface in the monolayer. Furthermore, absorption and fluorescence spectroscopy showed that the isolated electronic properties of the pyrene units are intact even in a condensed state in the monolayer.

Air↗
PubMed2006

Parallel assembly of dipolar columns composed of a stacked cyclic tri-beta-peptide.

A novel cyclic trimer of a beta-amino acid, trans-2-aminocyclohexylcarboxylic acid, was synthesized and its conformation and ability to form assemblies investigated. FT-IR and NMR measurements and computational calculations showed that this cyclic tri-beta-peptide has a C3-symmetric conformation with trans amide groups. A notable feature of the conformation is a vertical and parallel orientation of the three amide groups to the cyclic skeleton. The cyclic tri-beta-peptide was crystallized from a solution in trifluoroacetic acid-methanol (or trifluoroacetic acid-water) to yield a rod-shaped molecular assembly, as observed by TEM. The electron crystallography of the rod-shaped assembly both in suspension and in ultrathin cross-section revealed that the cyclic tri-beta-peptides were stacked up to form molecular columns, and that a two-fold screw symmetry operation along the column direction was present in the unit cell, which contained two cyclic tri-beta-peptides. This indicates that all the amide groups are oriented in the same direction. Since any two molecular columns are staggered by a quarter of a c-axis length and aligned parallel to each other, the dipole moments of the columns are aligned to enhance the strength additively in the whole assembly.

Crystallization↗
PubMed2006

Columnar assembly of cyclic beta-amino acid functionalized with pyranose rings.

A novel cyclic trimer and tetramer of protected beta-glycamino acids were synthesized and investigated on conformation and assembly formation. A characteristic point of these cyclic beta-glycamino acids is their better solubility than other cyclic beta-amino acids due to the pyranose rings. Thus, the assembling process of the cyclic molecules could be examined by CD or NMR spectroscopy. FT-IR and NMR measurements and geometry optimization revealed a highly symmetric and planar conformation for each cyclic beta-peptide with all-trans amide groups. The amide groups in the cyclic peptides took a vertical orientation against the cyclic skeleton to be suitably arranged for intermolecular hydrogen bonds, which should promote formation of molecular assembly in a columnar structure through molecular stacking. These cyclic beta-peptides were successfully crystallized to yield rod-shaped molecular assemblies in nanometer sizes. Evidence for the columnar structure in the crystals was obtained by electron diffraction analysis, which showed a layer spacing of ca. 4.8 A. Interestingly, the molecular assembly of the cyclic trimer showed a high aspect ratio, width less than 40 nm, and length more than 2 mum, suggesting stable molecular stacking in the column.

Amino Acids↗
PubMed2006

Histopathological and immunohistochemical findings in a case of glycogen-rich clear cell carcinoma of the breast.

Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare variant of primary breast carcinoma that was first described by Hull et al. in 1981, and is characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. The present case involved a 33-year-old female. She had noticed a lump in the inner quadrant of the left breast. The tumor obtained by enucleation biopsy had an irregular shape. The tumor cells exhibited sharply defined borders, polygonal contours, a clear or finely granular cytoplasm, and moderate nuclear atypia. The tumor cells showed a positive reaction with periodic acid Schiff, eliminated by diastase digestion. The tumor was diagnosed as GRCC. There was no nodal metastasis. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, HER2, and p53, but negative for estrogen receptor (ER) and progesterone receptor (PR). Although the biological behavior of GRCC is difficult to predict in view of the very limited number of case reports, the prognosis of GRCC may be associated with not only histopathological subtype but also other clinicopathological factors, such as size, status of invasion, status of nodal metastasis, nuclear grade, ER, PR, HER-2, p53 and so on. To clarify the pathogenesis of mammary GRCC, the systematic study of additional well-documented cases with long-term follow up will be necessary.

Adult↗
PubMed2005

Electron transfer in metal-molecule-metal junction composed of self-assembled monolayers of helical peptides carrying redox-active ferrocene units.

Electronic properties of three kinds of helical peptides with or without redox-active ferrocene units were investigated by using scanning tunneling microscopy under ultrahigh vacuum. The currents through the helical peptides carrying ferrocene units at the molecular terminals became significantly larger than that through a reference peptide without any ferrocene units. On the other hand, ferrocene units in the middle of the peptide chain did not affect the current-voltage characteristics. These results indicate that the ferrocene units near the metal electrode should play an important role for efficient electron transfer between the metal and the peptide molecules, which process is one of the rate-determining steps for characterizing molecular conductance in metal-molecule-metal junction.

Electrons↗
PubMed2005

pH-controlled switching of photocurrent direction by self-assembled monolayer of helical peptides.

A novel molecular system, where the photocurrent direction can be reversibly switched by changing the pH of the solution, was prepared on gold from helical peptides carrying a photosensitizer and a carboxyl group at the terminal. Upon photoexcitation of the photosensitizer in an aqueous solution containing an electron donor and acceptor at pH 10, the monolayer generated an anodic photocurrent due to enhancement of the dipole moment by a carboxylate anion, while it generated an opposite cathodic photocurrent at pH 3.4

Hydrogen-Ion Concentration↗
PubMed2005

Effects of dipole moment, linkers, and chromophores at side chains on long-range electron transfer through helical peptides.

Octadecapeptides carrying a ferrocene moiety at the molecular terminal were self-assembled on gold, and long-range electron transfer from the ferrocene moiety to gold was investigated by electrochemical methods. Effects on electron transfer of dipole moment of helical peptides, linkers connecting the peptide to gold, and chromophores introduced into the side chains were discussed. Cyclic voltammetry of the monolayers in an aqueous solution revealed that long-range electron transfer over 40 A occurred along the peptide molecule. Chronoamperometry showed that the long-range electron transfer should be ascribed to a hopping mechanism with use of amide groups as hopping sites. Electron transfer through the long peptide was not significantly accelerated by the dipole moment. However, the linker remarkably affected electron transfer depending on whether it was a methylene chain or a phenylene group, suggesting that local electron transfer between gold and the peptides should be the slowest step to determine the overall rate. Pyrenyl groups introduced into the side chains in the middle of the peptide molecule did not noticeably change electron transfer, probably because pyrenyl groups were too distant to allow direct electron transfer between them. Electrostatic potential profiles across the peptide monolayers were also calculated to explain reasonably the several interesting features in the present peptide systems.

Cross-Linking Reagents↗
PubMed2005

Molecular rectification of a helical peptide with a redox group in the metal-molecule-metal junction.

A helical hexadecapeptide immobilized on gold via a thiophenyl group at the N-terminal was analyzed by scanning tunneling microscopy under ultrahigh vacuum to obtain the I-V response at a molecular level. The attenuation factor of the electron transfer through the hexadecapeptide was determined by applying the Simons model to the I-V response to show better molecular conductance of the hexadecapeptide than dodecanethiol. Chemical modification at the C-terminal of the hexadecapeptide with a ferrocene unit, on the other hand, brought about significant changes in the I-V response, where the helical peptide became more conductive at the negative bias voltage. The molecular rectification behavior is due to the ferrocene unit regulating the direction of the electron transfer at the metal-molecule junction.

Aminoisobutyric Acids↗
PubMed2005

A good model of hepatic failure after excessive hepatectomy in mice.

AIMS: This study was intended to establish in mice: 1) a safety limit for the extent of hepatectomy and 2) the extent of hepatectomy invariably causing fatal hepatic failure, to facilitate gene expression analysis. MATERIALS AND METHODS: In 70%-hepatectomy, the left lateral and median lobes were removed, and in 90%-hepatectomy, all lobes except the caudate were resected. One-week survival rates, serum concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin were measured. Histological examinations were performed using hematoxylin and eosin staining, and immunohistochemical tests were done with antibody against Ki-67 antigen. RESULTS: All of the 70%-hepatectomized mice were alive at 1 week, but the 90%-hepatectomized mice all died within 24 h after hepatectomy. Serum aminotransferase and total bilirubin levels were significantly higher in the 90%-hepatectomized mice than in the 70%-hepatectomized mice. Liver histology revealed more prominent vacuolar degeneration in the former. Ki67-positive hepatocytes appeared and proliferated immediately after 70%-hepatectomy, but few were observed in the 70%-hepatectomized mice. CONCLUSION: We established 90%-hepatectomy as the safety limit for murine hepatectomy and as a model for liver regeneration, and 90%-hepatectomy as a "fatal hepatic failure level."

Alanine Transaminase↗
PubMed2004

Formation of gold nanoparticles in microreactor composed of helical peptide assembly in water.

A novel microreactor was prepared by self-assembly of an amphiphilic block copolymer composed of a hydrophobic helical peptide unit with a naphthyl group at the C terminal and a hydrophilic poly(ethylene glycol) unit. The copolymer formed a self-assembly in water, taking a vesicular structure. Noticeably, when the copolymer was dispersed in an Au(3+) aqueous solution, gold nanoparticles were formed without addition of any reducing reagent. The naphthyl groups, which are located at the inner surface of the vesicular assembly, promoted the reduction of Au(3+) ions with accompanying pH decrease.

Cations↗
PubMed2004

Efficient photocurrent generation by self-assembled monolayers composed of 3 10-helical peptides carrying linearly spaced naphthyl groups at the side chains.

Self-assembled monolayers (SAMs) were prepared on a gold substrate from a 310-helical peptide carrying three naphthyl groups at the side chain (SSN3B) or from the reference peptides carrying no or one naphthyl group. The 310-helical conformation of SSN3B in solution was confirmed by 1H NMR spectroscopy and geometry optimization. Cyclic voltammetry and infrared absorption-reflection spectroscopy showed vertical molecular orientation and a well-packed structure in the SSN3B SAM. Anodic photocurrent was successfully generated by the SSN3B SAM in the presence of triethanolamine, and the current intensity was found to be much larger than those by the other SAMs from peptides carrying one naphthyl group. It was therefore concluded that the linearly spaced naphthyl groups along the helical axis act as photosensitizer and electron-hopping site to promote photocurrent generation remarkably.

Aminoisobutyric Acids↗
PubMed2004

A molecular photodiode system that can switch photocurrent direction.

We prepared a molecular photodiode system in which the photocurrent direction can be switched by choosing the wavelength of an irradiating light. The molecular system is composed of two types of helical peptides that carry different chromophores and have different directions of dipole moments when they are immobilized on gold. The mixed, self-assembled monolayer generated an anodic photocurrent when one of the two chromophores was photoexcited, whereas the photocurrent switched to being cathodic when the other chromophore was photoexcited. The opposite current response arises from the dipole moment of each helical peptide, which accelerates electron transfer in the same direction.

Journal Article↗
PubMed2004

Telomerase activity and Bcl-2 expression in gallbladders of pancreaticobiliary maljunction patients: a preliminary study.

BACKGROUND: The congenital anomaly pancreaticobiliary maljunction (PBM) is considered to be a precancerous disease. PBM carcinogenesis is believed to be an accumulation of gene abnormalities, but the early events causing PBM carcinogenesis are still unclear. In the present study, telomerase activity and Bcl-2 expression in the gallbladder mucosa of PBM and non-PBM gallbladders were investigated. METHODS: The operative gallbladder materials were from five control cases, two cases of non-PBM gallbladder cancer, three of PBM gallbladder cancer, and three of non-neoplastic PBMs. Multiple sampling was performed from each gallbladder. The studies performed were: (1) immunohistochemistry of p53, Ki-67, and Bcl-2; (2) survey of k-ras point mutations; and (3) measurement of telomerase activity in each sample. RESULTS: In the cases of non-PBM cancer, abnormalities from the above studies were detected only in the cancerous lesions. Normal-appearing mucosa did not show Bcl-2 expression or telomerase activity. However, in the cases of PBM cancer, normal-appearing mucosa showed telomerase activity and Bcl-2 expression, but did not show p53, Ki-67, or k-ras abnormalities. In the non-neoplastic PBM, all samples showed Bcl-2 expression, and many showed telomerase activity. CONCLUSIONS: Bcl-2 expression and activation of telomerase are probably early events causing carcinogenesis of the PBM gallbladder mucosa. They might be important factors causing carcinogenesis associated with chronic inflammation.

Gallbladder↗
PubMed2004

Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray.

BACKGROUND/AIMS: The liver has the capacity to regenerate after partial hepatectomy. In order to clarify the mechanism of liver regeneration, we observed the initial stage, especially the mechanism of gene expression during progress from G0 to S phase (0-24 h), and attempted to identify new genes controlling progress to the S phase. METHODS: We applied large-scale gene expression analysis with complementary DNA microarrays in mouse hepatectomy models to clarify the mechanism of liver regeneration after partial hepatectomy. RESULTS: As a result, 23 new immediate-early gene candidates such as interleukin-1 receptor associated kinase-1 and karyopherin alpha-1, which are involved in transportation within the nucleus, were discovered. Candidates for new genes concerned with the progress to the S phase were discovered: inhibitor of DNA binding 2 (ID2) and inhibitor of DNA binding 3 (ID3), both new liver regeneration factors that promoted progress to the S phase, and GADD45 gamma (growth arrest and DNA-damage-inducible protein) as a factor inhibiting that process. CONCLUSIONS: The above results not only suggest the importance of NFkappaB in the initial stage of liver regeneration but also points to the orderly maintenance of the proliferation of the cells in liver regeneration.

Animals↗
PubMed2003

Long-range electron transfer over 4 nm governed by an inelastic hopping mechanism in self-assembled monolayers of helical peptides.

Well-ordered self-assembled monolayers (SAMs) were prepared on gold from helical peptides carrying a ferrocene (Fc) moiety at the N- or C-terminal end, and long-range electron transfer (ET) from Fc to gold was investigated. Electrochemical studies revealed that an inelastic hopping mechanism dominated over the superexchange mechanism in the ET reactions in the present SAMs and the dipole moment of the helix accelerated the ET reactions probably due to the lowering of the barrier height between the gold surface and peptide layer.

Disulfides↗
PubMed2003

Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of 'molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as "unknown EST," and 1969 (58%) clones of 3388 clones that were categorized as "unclassifiable" were also shown to be reproducibly expressed.

Animals↗
PubMed2002

Identification of genes regulating colorectal carcinogenesis by using the algorithm for diagnosing malignant state method.

We studied the expression profiles of various stages of colorectal tumors (adenoma (AD), seven samples; carcinoma (CA), 16 samples) by using cDNA microarrays and developed ADMS (algorithm for diagnosing malignant state) method, selecting 335 clones characteristic of CA state. We, then, applied ADMS to 12 additional samples (five from primary lesions with metastasis and seven metastases); all 16 CAs and 12 metastatic tumors were diagnosed correctly as cancerous states. Although three of the seven ADs were diagnosed as "cancerous," the large size of two of these tumors suggested their potential malignancy. Our strategy for selecting clones characteristic of the malignant state is widely applicable to diagnosis and for predicting the stage of progression during multistep carcinogenesis. Of the 335 clones we selected, 135 were known genes. Included in the 135 genes were tumor suppressor and growth factor-related genes and were consistent with the literature. ADMS is a reliable means for identifying genes useful for the diagnosis of cancer.

Adenoma↗