巻号一覧
50 巻 (2002)
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50 巻, 3 号
選択された号の論文の7件中1～7を表示しています
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応用講座 I 脂質メディエーター研究へのMSの利用
総説
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徳村 彰2002 年 50 巻 3 号 p. 100-107
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーStructures of phosphatidylcholines having an oxidatively shortened fatty acyl group resemble that of the platelet-activating factor (PAF), a chemical mediator of inflammation, and therefore they are classified as PAF-like lipids. Gas chromatography-mass spectrometry has been utilized for analysis of the class, subclass and molecular species compositions of PAF-like lipids, providing usefel informations on mechanisms of their formation. Gas chromatography-mass spectrometry was also found to be useful for the determination of lysophosphatidic acid, a growth factor in animal plasma, and clarification of mechanisms of its formation.抄録全体を表示PDF形式でダウンロード (877K)
応用講座 II（その1） 新世紀生命科学におけるプロテオミクスとMSの役割
総説
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松本 博行, 黒野 定, 小森 直香2002 年 50 巻 3 号 p. 116-125
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーA proteomics approach to the study of protein expression and post-translational modification does not require presumptions of the identity of target proteins. A proteomic investigation begins with the discovery of unidentified proteins of interest under well-defined physiological conditions. The approach involves 1) protein display by two-dimensional gel electrophoresis or other separation technique, 2) determination of protein entities, 3) peptide mass fingerprinting, and 4) genome/proteome database search. We show that the methodology of the proteomics approach is characterized neither by deduction nor by induction in the traditional sense, but is a clear example of what C. S. Peirce described as abductive inference almost a century ago. The investigation of complex signaling pathways is intractable to deductive and inductive methods due to its extreme complexity. We show two cases of the proteomics approach as applied to the visual systems of the fruit fly Drosophila melanogaster, and rodents. These examples illustrate the role of abductive inference in proteomics, a discipline at the forefront of current studies in molecular biology.抄録全体を表示PDF形式でダウンロード (2243K)
応用講座 II（その2） プロテオミクス実践講座
解説
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片山 博之, 小田 吉哉2002 年 50 巻 3 号 p. 126-134
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーAlthough the word “Proteome” also appeared in 1995 for the first time, it was hardly observed at that time. On the other hand, some papers about a microarray were released at the same time. The microarray has spread in an instant, and although there is the side in which it is troubled by the interpretation for too much a vast quantity of data, the information which transcriptomics brings about is achieving success certainly, and greatly has begun to contribute not only to drug discovery but to the life science field. Then, how is it about proteomics? Although the result has appeared in the search for a clinical marker for a serum sample without genome, there is almost no example of a success which contributed to life science in proteome analysis. In a transcriptomics and proteomics, a difference is in the amount of information acquired too much. The current proteomics understands only a part very much. Furthermore, proteomics is greatly inferior also in through-put. Just the information which cannot be acquired only from a gene is considered to be the directivity of future proteomics. Therefore, we should focus on protein-complex analysis, post-translational modification study etc. and then should contribute to life science by performing more practical proteomics. The key of future proteomics is pursued not only in proteomics but in all fields about high speed, quantity sensitivity, automation, and information processing. Since it has already turned into fixed form business about identification of the protein using MS, it is a point how it utilizes well in a life science field. Application of chemical design like ICAT and genetic design like TAP are expected in a technical side. And breakthroughs, such as development of a protein chip which is located in a line with a DNA chip, and an amplification means of the protein equivalent to PCR, may also appear suddenly.抄録全体を表示PDF形式でダウンロード (893K) -
川上 隆雄, 安養寺 久栄, 西村 俊秀2002 年 50 巻 3 号 p. 135-141
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーIn the post-genome era, there is an immediate requirement for the analysis of proteome, which gives a great impact on the methodology of disease diagnosis and drug discovery in medicine and pharmaceutical sciences. Mass spectrometry (MS) is essential for high throughput and accurate detection/identification of potential drug target proteins in low abundance localized to intrinsic functions at the extremely early stage of disease progression. Conventional proteome analysis strategy with two-dimensional electrophoresis (2-DE) techniques is not compatible for the drug discovery process and MS analysis, mainly due to poor solubility of many hydrophobic proteins in the current 2-DE sample buffers and its drawbacks including being low reproducibility, time consuming and very labor intensive. Higher throughput identification of proteins, including membrane-binding ones, was accomplished by introducing one-dimensional (1D) sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for protein fractionation coupled with nano-liquid chromatography (nanoLC)/nano-electrospray ionization (nanoESI)/ion trap (IT)-MS/MS. Toward fully automated proteome analysis, a five-dimensional (5D)-LC-based system was constructed, consisting of two-dimensional LC for protein fractionation, followed by proteolytic fragmentation of each protein fraction, and two-dimensional nanoLC for peptide fractionation directly linked with nanoESI/IT-MS/MS. A combination of the isotope-coded affinity tags (ICAT) assay with 1D-SDS-PAGE fractionation or the 5D-LC proteome workstation followed by nanoESI/IT-MS/MS data-dependent measurements under the dynamic exclusion mode will bring a promising approach for identification and quantification of proteins expressed in a disease progression. This strategy leads to the high throughput discovery of key target components related to disease progression or origin.抄録全体を表示PDF形式でダウンロード (1112K) -
山田 尚之2002 年 50 巻 3 号 p. 142-147
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーFourier-transform ion cyclotron resonance-mass spectrometer (FTICR-MS) is a new instrument which has the feature with ultra high-resolution and high mass accuracy. In addition, there is a possibility that the fragmentation of the whole protein can be generated by using the some techniques such as capillary-skimmer CID, hexapole-CID, IRMPD, ECD, and BIRD in FTICR-MS. In the present commentary, it will be described about the feature of FTICR-MS, and the latest application example to proteomics field.抄録全体を表示PDF形式でダウンロード (665K)
応用講座 III 最近の薬物動態研究とMS
解説
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渡部 烈, 小倉 健一郎2002 年 50 巻 3 号 p. 155-161
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーIn 1993, there were 18 acute deaths in Japanese patients who had the viral disease, herpes zoster, and were administered with a new anti-viral drug, sorivudine (SRV, 1-β-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil). All the dead patients were receiving a 5-fluorouracil (5-FU) prodrug for anti-cancer chemotherapy when they were administered with SRV. Studies on toxicokinetics in rats and on their hepatic dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme for the 5-FU catabolism in the rat and human, strongly suggested that in the patients who received both SRV and 5-FU prodrug, tissue levels of highly toxic 5-FU increased extremely as a result of irreversible inactivation of DPD in the presence of NADPH by 5-(2-bromovinyl)uracil (BVU), a metabolite formed from SRV by gut flora in rats and humans. Recombinant human (h) DPD was also irreversibly inactivated by [14C]BVU in the presence of NADPH. MALDI-TOF MS analysis of radioactive tryptic fragments from the radiolabeled and inactivated hDPD demonstrated that a Cys residue located at position 671 in the pyrimidine-binding domain of hDPD was modified with an allyl bromide type of reactive metabolite, dihydro-BVU.抄録全体を表示PDF形式でダウンロード (1209K)
総合論文
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眞野 成康, 池川 繁男, 後藤 順一2002 年 50 巻 3 号 p. 162-170
発行日: 2002年
公開日: 2007/10/16
ジャーナル フリーIn the body, drugs and biological active substances having a carboxyl group in those molecules have been known to transform various metabolites. Commonly, these compounds such as α-aryl propionic acid derivatives are activated to corresponding intermediates like a coenzyme A thiol ester prior to both isomerizations and conjugations with amino acids. The acyl adenylate has been also noted as an intermediate of coenzyme A ligation. In addition, the carboxyl group is known to be metabolized to acyl glucuronides in hepatocyte. Both the acyl adenylate and the acyl glucuronide are chemically very active, and they may produce the protein-bound adducts by reaction with the nucleophilic groups such as an amino group on the protein molecule. The authors have synthesized acyl glucuronides and acyl adenylates of bile acids, which are endogeous carboxylic acid derivatives, biosynthesized from cholesterol in the hepatocyte, and investigated their reactivity with peptide or protein. Both results clearly indicated that these active intermediates produced protein-bound adducts nonenzymatically. The formation of such adducts has attracted attention as a possible explanation for hypersensitivity, and non-enzymatic post-translational modifications to proteins in the body.抄録全体を表示PDF形式でダウンロード (1168K)
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