著者

谷野 哲也 市川 聡 魚谷 幸一 大山 洋 松田 彰

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.3, pp.335-346, 2011 (Released:2011-03-01)

参考文献数

34

被引用文献数

2 2

---

This review describes the synthesis and structure-activity relationship (SAR) study of muraymycins (MRYs), which are potent antibacterial nucleoside antibiotics. The key elements of our synthetic approach include the preparation of L-epi-capreomycidine via a C-H amination reaction and a convergent assemblage to construct of the framework of MRYs using Ugi four component reaction. With this approach the first total synthesis of MRY D2 and its epimer, epi-MRY D2, which does not have lipophilic substituents, has been accomplished. The fact that MRY D2 and it's epimer did not show any antibacterial activity indicated the lipophilic substituents of MRYs plays an important role in membrane-permeability. Hence, MRY analogues with lipophilic substituents were designed and synthesized simply by altering the aldehyde component in Ugi four-component assemblage. The MRY analogues with lipophilic substituents exhibited improved antibacterial activity against anti drug-resistant bacteria. It was also suggested that the accessory urea-dipeptide motif might contribute to MraY inhibitory and antibacterial activity. Our synthetic approach would effectively provide a variety of MRY analogues and resultant SAR information brings us directions to create further MRY analogues.

著者

今戸 佐太郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.81, no.6, pp.828-832, 1961-06-25 (Released:2010-02-19)

参考文献数

2

---

trans-Bis (N-ethylidene-DL-threoninato) copper (II) dihydrate comes in α- and β-form crystals, both melting at 202-203° with decomposition. The α-form crystal is a monoclinic holohedral class and the β-form crystal belongs to the triclinic holohedral class, the α-form crystal having C2h-2/m and β-form, Ci-1. These crystals were proved to be polymorphic forms by their comparative examination through X-ray powder and chemical methods.

著者

稲垣 昌宣

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.8, pp.1187-1194, 2008-08-01 (Released:2008-08-01)

参考文献数

29

被引用文献数

2 7

---

Glycosphingolipids (GSLs) are contained in a various cell membranes and have recently been implicated in many physiologic functions. They are classified based on their sugar moieties into ceramides, cerebrosides, sulfatides, ceramide-oligohexosides, globosides, and gangliosides. A number of GSLs have been obtained from marine invertebrates such as echinoderms, poriferans, and mollusks and have unique biological activities. During the course of our search for biologically active GSLs from echinoderms, we conducted the isolation and structural elucidation of GSLs from starfish and feather stars and found numerous GSLs, some of which have unique structures. In particular, gangliosides from feather stars were unique in that the sialic acids bind to inositol-phosphoceramide. We also found that the GSLs from starfish and feather stars possess neuritogenic activity toward the rat pheochromocytoma cell line PC12, antihyperglycemic effects against type 2 diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice, and antiosteoporosis effects toward the osteoporosis model mice (OVX mice). These biological activities are thought to be related to dementia, osteoporosis, and diabetes, which are becoming social problems, and are expected to become the seeds of preventive or therapeutic drugs for these illness.

著者

山田 耕史

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)

巻号頁・発行日

vol.122, no.12, pp.1133-1143, 2002-12-01

参考文献数

67

被引用文献数

4 17

---

Glycosphingolipids (GSLs), together with glycopeptides, are typical constituents of various cell membranes in a wide variety of organisms. In particular, it is known that GSLs have numerous physiological functions due to variations in the sugar chain, in spite of the very small quantity of constituents. Those are classified into cerebrosides, sulfatides, ceramide oligohexosides, globosides, and gangliosides based on the constituent sugars. Gangliosides, sialic acid-containing GSLs, are especially enriched in the brain and nervous tissues and are involved in the regulation of many cellular events. Recently, a number of GSLs have been isolated from marine invertebrates such as echinoderms, poriferans, and mollusks. We have also been researching biologically active GSLs from echinoderms to elucidate the structure-function relationships of GSLs and to develop novel medicinal resources. This review summarizes the structures and biological activities of GSLs from sea cucumbers. This study showed that the characteristics of GSLs and structure-activity relationships had neuritogenic activity toward the rat pheochromocytoma cell line PC12. That is, most of the cerebroside constituents of the sea cucumber are same glucocerebrosides as in other animals, except for some constituents, while the ganglioside constituents were unique in that a sialic acid directly binds to the glucose of cerebroside, they are mutually connected in tandem, and some are located in the internal parts of the sugar chain. It also became apparent that sialic acid is indispensable for the neuritogenic activities.<br>

著者

豊田 正夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.12, pp.1359-1372, 2000-12-01 (Released:2008-05-30)

参考文献数

37

被引用文献数

1 8

---

Four hundred samples of Conocephalum conicum, collected in various places have been analyzed by GC-MS. This resulted in the presence of three chemo-types of C. conicum. One of them elaborate (-)-sabinene (type-I) as a major compound. The other two types characteristically contained (+)-bornyl acetate (type-II) and methyl cinnamate (type-III) as major constituent respectively. The structures of three new monoterpenic esters, isolated from the ether extract of C. conicum (type-I and/or II) have been established by chemical and spectral means. They were shown to be monoterpenic esters of (+)-borneol and p-coumaric acid derivatives. The ether extract of the liverwort Chiloscyphus polyanthos afforded sesquiterpenoids which are enantiomeric to those found in another liverwort Lepidozia vitrea. The absolute configurations of the sesquiterpenoids found in the C. polyanthos were determined by spectroscopic evidence, chemical derivatization and/or x-ray crystallographic analysis. The ether extract of the liverwort Porella perrottetiana afforded (-)-α-eudesmol, which showed an opposite sign of the optical rotation to that found in higher plants. Present work on the absolute configuration and an optical purity of (-)-α-eudesmol strongly suggested that the positive values (e.g.+28.5°) described in many previous papers should be revised. Since the absolute configuration of (-)-α-eudesmol was identical to that (+)-β-eudesmol found in the higher plants, it was apparent that the expression of the positive sign might be revised to (-)-α-eudesmol. The optical purity, reconfirmation of the absolute configuration and synthesis of (-)-α-eudesmol will be discussed.

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.74, pp.183-186, 1888-04-07

著者

小村 弘 松田 健一 茂本 友貴枝 河原 亥一郎 阿野 理恵子 村山 洋子 森脇 俊哉 吉田 長弘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.125, no.1, pp.131-139, 2005-01-01 (Released:2005-01-01)

参考文献数

25

被引用文献数

2 3

---

Metabolic screening using liver microsomes of rats and humans is an indispensable tool to optimize a lead structure and to select compounds for in vivo study. Elucidating the relationship between in vitro intrinsic clearance (CLint, app) and in vivo clearance (CLb) is a prerequisite for screening. We investigated the relationship between CLint, app in rat liver microsomes and CLb after intravenous administration in rats in eight projects. No relationship between these two parameters was found across all of the projects examined. However, there was a certain relationship in the same core structure of six projects, but not in the other two projects. The poor correlation in the projects was improved by considering serum protein binding or microsomal binding in the estimation of in vitro clearances. Although the binding assay was labor intensive, unlike metabolic screening, the introduction of the equilibrium dialysis method using a 96-well format increased the throughput. Optimization of metabolic stability was conducted on the basis of the structure-metabolic stability relationship (SMR) in one of the projects, showing a good correlation without the binding factors. The replacement of the piperazine with a homopiperazine moiety improved metabolic stability in the rat and human liver microsomes. The compound also showed a desirable in vivo pharmacokinetic profile in rats, suggesting that the SMR study on the confirmed in vitro and in vivo correlation is essential to the optimization.

著者

伊東 祐二

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.7, pp.823-830, 2017 (Released:2017-07-01)

参考文献数

15

被引用文献数

2

---

As an alternative to hybridoma technology, the antibody phage library system can also be used for antibody selection. This method enables the isolation of antigen-specific binders through an in vitro selection process known as biopanning. While it has several advantages, such as an avoidance of animal immunization, the phage cloning and screening steps of biopanning are time-consuming and problematic. Here, we introduce a novel biopanning method combined with high-throughput sequencing (HTS) using a next-generation sequencer (NGS) to save time and effort in antibody selection, and to increase the diversity of acquired antibody sequences. Biopannings against a target antigen were performed using a human single chain Fv (scFv) antibody phage library. VH genes in pooled phages at each round of biopanning were analyzed by HTS on a NGS. The obtained data were trimmed, merged, and translated into amino acid sequences. The frequencies (%) of the respective VH sequences at each biopanning step were calculated, and the amplification factor (change of frequency through biopanning) was obtained to estimate the potential for antigen binding. A phylogenetic tree was drawn using the top 50 VH sequences with high amplification factors. Representative VH sequences forming the cluster were then picked up and used to reconstruct scFv genes harboring these VHs. Their derived scFv-Fc fusion proteins showed clear antigen binding activity. These results indicate that a combination of biopanning and HTS enables the rapid and comprehensive identification of specific binders from antibody phage libraries.

著者

石井 明子 津本 浩平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.7, pp.815-816, 2017 (Released:2017-07-01)

著者

石原 慶一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.7, pp.807-810, 2017 (Released:2017-07-01)

参考文献数

8

---

Down syndrome, caused by the triplication of human chromosome 21, is the most frequent genetic cause of mental retardation. Mice with a segmental trisomy for mouse chromosome 16, which is orthologous to human chromosome 21, exhibit abnormalities similar to those in individuals with Down syndrome and therefore offer the opportunity for a genotype-phenotype correlation. In the current review, I present several mouse lines with trisomic regions of various lengths and discuss their usefulness for elucidating the mechanisms underlying Down syndrome-associated developmental cognitive disabilities. In addition, our recent comprehensive study attempting to identify molecules with disturbed expression in the brain of a mouse model of Down syndrome in order to develop a pharmacologic therapy for Down syndrome is described.

著者

小島 正美

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.5, pp.555-559, 2012

---

A lot of healthcare professionals experienced annoyance with biased mass media news regarding medical and health issues. In this paper, I propose "news profiling method" and "media guideline" to improve the medical and health journalism.<br>

著者

太田 邦史 瀬尾 秀宗

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.127, no.1, pp.81-89, 2007-01-01

被引用文献数

1 2

---

Monoclonal antibodies (MAbs) have been utilized as research tools, as diagnostic reagents, and for antibody medicine. The preparation of MAbs involves laborious processes and normally takes months. Here we describe an ex vivo B cell-based antibody display system called the ADLib (Autonomously Diversifying Library) system, which enables us to select chicken B cell clones producing antibody against antigens of interest in a couple of weeks. The ADLib system is applicable to self- or highly conserved antigens, polysaccharide chains, peptides, and haptens.

著者

杉本 八郎 山西 嘉晴 小倉 博雄 飯村 洋一 山津 清實

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.119, no.2, pp.101-113, 1999-02-01 (Released:2008-05-30)

参考文献数

28

被引用文献数

3 9

---

The most consistent change of neurotransmitter in the brain of Alzheimer's patients is the dramatic decrease of cholinergic innervation due to the loss of neurons in the basal forebrain. The most widely studied acetylcholinesterase inhibitors (AChEIs) have been physostigmine and tacrine. Physostigmine has very short duration, and tacrine has liability to hepatotoxicity. These are the defects of the inhibitors. Our objective was to find a new type of AChEIs that would overcome the disadvantages of physostigmine and tacrine. Through a random screening, we incidentally found an N-benzylpiperazine derivative which showed positive cholinergic behavior in rats. We replaced the N-benzylpiperazine moiety with N-benzylpiperidine moiety and found a dramatic increase in anti-AChE activity. Even after the replacement of an amide group with a ketone group the activity was held. Furthermore, the cyclic-amide derivative showed enhanced inhibitory activity. On the basis of these results, an indanone derivative was designed. Among these indanone derivatives, donepazil hydrochloride (E2020), brand name ARICEPT was found to be the most balanced compound. The clinical studies of donepezil hydrochloride demonstrated statistically significant effects on ADAS-cog (Alzheimer's Disease Assessment Scale cognitive sub.) and CIBIC Plus (Clinician's Interview-Based Impression of Change plus).

著者

谷村 顕雄 秦 邦男 竹下 隆三

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.84, no.7, pp.652-655, 1964-07-25 (Released:2010-02-19)

参考文献数

11

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Analysis was made on the composition of torula yeast, prepared from sulfite pulp waste liquor, using Torulopsis utilis, in order to elucidate the factor accelerating animal growth. Ethanol extract of torula yeast was fractionated and examination was made on several crystalline substances obtained. Besides D-galactose, ergosterol, and myristic acid, 1, 2, 3, 5, 6-penta-O-acetyl-α-D-galactofuranose was obtained in 0.11% yield. This is the first example of its presence in a natural product and it is interesting that a substance with so many acetyl groups had been found in nature.

著者

芝 清隆

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.11, pp.1295-1302, 2009 (Released:2009-11-01)

参考文献数

26

被引用文献数

1 1

---

Motif-programming is a method for creating artificial proteins by combining functional peptide motifs in a combinatorial manner. Motifs are often short amino acid sequences within natural proteins that are associated with particular biological functions. Motifs also can be created de novo using molecular engineering. In particular, peptide aptamers, which have been isolated as specific binders against various targets, are believed to be promising motif blocks for creating novel biomaterials through motif-programming. It is now known, however, that simple arithmetic addition does not always work with motif-programming-e.g., simple conjugation of motifs-A and -B does not always result in a bifunctional peptide-AB. To solve this nonlinearity in motif-programming, we have been employing a combinatorial approach, which we called MolCraft. In MolCraft, we prepare a library of artificial proteins that contain multiple motifs in various numbers and orders, from which clones having the desired functions are selected. In MolCraft, a microgene is first rationally designed so that the encoded peptides contain motifs, and then tandemly polymerized with insertion or deletion mutations at the junctions between microgene units. Because of junctional perturbations, proteins translated from a single microgene polymer are molecularly diverse, originating from the combinatorics of three reading frames, and are thus combinatorial polymers of three peptides. By embedding functional motifs into different reading frames of a single microgene, combinatorial polymers of functional motifs are easily prepared. Notably, repetitiousness retained in the overall structure of proteins contributes to the formation of ordered structures, and enhances the chances of reconstituting biological activity. This method is particularly well suited for developing liaison molecules that interface between cells and inorganic materials. Examples of multifunctional artificial proteins created from this method will be introduced.

著者

谷内 信彦 新留 徹広 杉本 八郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.2, pp.323-329, 2015-02-01 (Released:2015-02-01)

参考文献数

36

被引用文献数

1 1

---

In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation.

著者

古瀬 幹夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.134, no.5, pp.615-621, 2014 (Released:2014-05-01)

参考文献数

13

被引用文献数

1

---

Within an epithelial cellular sheet, the paracellular pathway can be divided into two routes: one between two adjacent cells and one at tricellular contacts, where the vertices of three cells meet. For epithelial barrier function, tight junctions restrict solute permeability through the paracellular pathway between two cells, while tricellular contacts contain specialized structures of tight junctions, named tricellular tight junctions (tTJs). Two types of membrane proteins, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2) have been identified as molecular components of tTJs. Angulins recruit triellulin to tTJs and these tTJ-associated proteins are required for normal tTJ formation as well as strong epithelial barrier function. Furthermore, mutations in tricellulin and angulin-2/ILDR1 genes cause autosomal recessive familial deafness, DFNB49 and DFNB42, respectively. Further analyses of the angulin-tricellulin system should lead to better understanding of the molecular mechanism and regulation of tTJs.

著者

二宮 忠八

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.254, pp.328-332, 1903-04-26

著者

上野

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.160, pp.509-510, 1895-06-26

著者

飯嶋 久志 大澄 朋香 小清水 敏昌

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.9, pp.1215-1223, 2010 (Released:2010-09-01)

参考文献数

71

被引用文献数

2 2

---

In recent years, Evidence-based Medicine is practiced in medical care, and meta-analysis is positioned as the highest quality research paper. However, there are no unified criteria to evaluate meta-analysis. Thus, we developed and evaluated objective criteria of meta-analysis paper. Meta-analysis was evaluated from the standpoint of format and quality. Format score was developed based on QUOROM statement. Quality scores were evaluated in each step of meta-analysis. We evaluated meta-analysis for advantageous or adverse effect in the relationship between Renin-angiotensin system (RAS) inhibitor and diabetes mellitus. Research articles either in English or Japanese were searched in PubMed and the Cochrane Library in July 2009. Fifty-five studies were evaluated for format and quality score. Format score was 64.5±25.3% (Mean±S.D.), and quality score was 57.1±21.6%. After plotting each score along the X-Y coordinate, format score was correlated with quality score (R2=0.702, p<0.001). In studies with quality score of 70% or higher, RAS inhibitor prevented new-onset diabetes mellitus. Angiotensin converting enzyme (ACE) inhibitor reduced risk of myocardial infarction, however, angiotensin receptor blockers (ARB) increased the incidence in odds ratio 1.21 (95%CI: 1.04-1.40). We evaluated meta-analysis by format and quality score, and these factors showed correlation. Therefore, assessment of quality score leads to prompt and reliable evaluation of meta-analysis. According to articles evaluated by quality score, RAS inhibitor showed effectiveness on diabetes mellitus. However, careful attention must be given in ARB therapy on patients with myocardial infarction risk.