ペプチド合成研究45年の回顧
スポンサーリンク
概要
- 論文の詳細を見る
This review documents my research for the past 45 years in peptide chemistry. Initially, in order to study the structure-activity relationships of active center of α- and β-melanocyte stimulating hormones (H-His-Phe-Arg-Trp-Gly-OH), we employed D-amino acids. That approach yielded first published report in 1965 of antagonists containing D-amino acids. Monkey β-melanocyte stimulating hormone (β-MSH), an 18 amino acid peptide stimulated pigment cells. We synthesized β-MSH and fragments thereof, and studied in detail structure-activity relationships. A major and valuable result revealed that the C-terminal pentadecapeptide of β-MSH exhibited higher MSH activity than the parent hormone providing a new question; namely, what was the role of the N-terminal tripeptide? In order to identify the novel enzyme, spleen fibrinolytic proteinase (SFP), I developed a specific chromogenic substrate, Suc-Ala-Tyr-Leu-Val-pNA, and a specific inhibitor, Suc-Tyr-D-Leu-D-Val-pNA, once again employing my D-amino acid strategy. SFP was purified by affinity chromatography using Suc-Tyr-D-Leu-D-Val-pNA as the bound ligand. The success of this approach provided me the incentive to develop a variety of potential drugs. Thus, I prepared a specific plasmin inhibitor (YO-2) and a plasma kallikrein inhibitor (PKSI-527). Next, my research developed novel opioid receptor specific opioid agonists and antagonists based on 2′,6′-dimethyl-L-tyrosine (Dmt) dimers coupled with unique pyrazinone ring as a spacer. They exhibited potent oral antinociceptive activity acting through the μ-opioid receptor. Potent μ-receptor agonists (H-Dmt-Pro-Phe/Trp- Phe-NH2) were transformed into highly selective μ-receptor antagonists (N-allyl-Dmt-Pro-Phe/Trp-Phe-NH2), which reversed ethanol-induced increases in GABAergic neurotransmission, suggesting the possibility that they may emerge as candidates for the treatment of ethanol addiction.
- 公益社団法人 日本薬学会の論文
著者
関連論文
- Amino Acids and Peptides. XXXV. Synthesis of Mouse Metallothionein I. (2). Synthesis of a Nonacosapeptide Corresponding to N-Terminal Sequence 1-29 (β-Fragment) of Mouse Metallothionein I and Related Peptides and Examination of Their Heavy Metal-Binding P
- Amino Acids and Peptides. XXXIV. Synthesis of Mouse Metallothionein I. (1). Synthesis of Dotriacontapeptide Corresponding to C-Terminal Sequence 30-61 (α-Fragment) of Mouse Metallothionein I and Related Peptides and Examination of Their Heavy Metal-Bindin
- Amino Acids and Peptides. XXVII. : Synthesis of Phytochelatin-Related Peptides and Examination of Their Heavy Metal-Binding Properties
- Amino Acids and Peptides. XXVI. Synthesis of Agaricus bisporus Metallothionein and Related Peptides and Examination of Their Heavy Metal-Binding Properties
- Amino Acids and Peptides. XXIV. : Synthesis of Neurospora crassa Metallothionein and Related Cysteine-Containing Peptides and Examination of Their Heavy Metal-Binding Properties
- Amino Acids and Peptides. XXI. : Synthesis of N-Terminal Heptapeptide of Mammalian Metallothionein (MT) and Evaluation of Its Immunoreactivity
- Amino Acids and Peptides. XXXVII. Synthesis of Stereoisomeric Nonapeptides Corresponding to Sequence 41-49 of Eglin c and Examination of Their Inhibitory Activity against Human Leukocyte Cathepsin G and α-Chymotrypsin
- Application of Poly-L-lysine to Purification of Leukocyte Cathepsin G by Affinity Chromatography
- Amino Acids and Peptide. XXX. Synthesis of Eglin c (41-49) and Eglin c (60-63) and Examination of Their Inhibitory Activity towards Human Leukocyte Elastase, Cathepsin G, Porcine Pancreatic Elastase and α-Chymotrypsin
- Amino Acids and Peptides. XXIX. Synthesis of Peptide Fragments Related to Active Center of Eglin c and Studies on the Relationship between Their Structure and Their Inhibitory Activity against Cathepsin G and α-Chymotrypsin
- Amino Acids and Peptides. XXVIII. : Synthesis of Peptide Fragments Related to Eglin c and Studies on the Relationship between Their Structure and Effects on Human Leukocyte Elastase, Cathepsin G and α-Chymotrypsin
- Amino Acids and Peptides. XXII. : Synthesis of Substrates and Inhibitors of Human Leukocyte Cathepsin G
- Synthesis of Tripeptide Amide Derivatives and Examination of Their Inhibitory Effect on Human Leukocyte Elastase (HLE)
- Amino Acids and Peptides. XXXIX. Synthesis of iNoc-Gln-Val-Val-Ala-Ala-pNA and Its Action on Thiol Proteinases
- 中国製薬企業のR&Dとナレッジマネジメントに関する追跡調査
- 中国における製薬企業の研究開発マネジメントに関する実証研究
- 中国製薬企業の研究開発における地域の差 : 上海製薬企業の実態調査
- 製薬企業のナレッジマネジメントと研究開発に関する実態調査 : 中国の製薬企業5社を対象として
- 中国医薬品市場の発展と動向
- P-196 ムコソルバン^[○!R]錠と他剤との配合による変色の原因(12.品質管理・製剤試験,"薬剤師がつくる薬物治療"-薬・薬・学の連携-)
- 合成インヒビターのデザイン戦略 : 二機能性トロンビン阻害剤のデザイン
- 全国薬系大学防災状況アンケート調査 : 阪神・淡路大震災を踏まえて
- Amino Acids and Peptides. XL. Synthesis of Ac-Tyr-Val-Ala-Asp-MCA Using Newly Developed Acetylating Reagent
- Amino Acids and Peptides. XXXVI. Synthesis of Enkephalin Chloromethyl Ketone and Evaluation of Its Inhibitory Activity against Endopeptidase 22.19
- Development of Active Center-Directed Plasmin and Plasma Kallikrein Inhibitors and Studies on the Structure-Inhibitory Activity Relationship
- Synthesis of trans-4-Aminomethylcyclohexanecarbonyl-L- and -D-phenylalanine-4-carboxymethylanilide and Examination of Their Inhibitory Activity against Plasma Kallikrein
- Amino Acids and Peptides. XXXIII. Synthesis of N-Terminal Epitope Peptides of Mammalian Metallothioneins (MTs)
- Development of Selective Inhibitors against Plasma Kallikrein
- Development of Active Center-Directed Inhibitors against Plasmin
- Synthesis of Tripeptide Chloromethyl Ketones and Examination of Their Inhibitory Effects on Plasmin and Plasma Kallikrein
- Synthesis of Active Center-Directed Prptide Inhibitors of Plasmin
- Structure and Synthesis of an Immunoactive Lipopeptide, WS1279,of Microbial Origin
- STRUCTURE AND SYNTHESIS OF AN IMMUNOACTIVE LIPOPEPTIDE, WS1279,OF MICROBIAL ORIGIN
- Amino Acids and Peptides. XXV. : Application of Newly Developed β-1- and β-2-Adamantylaspartates to Peptide Synthesis by Solid Phase and Conventional Solution Methods
- 1-I-18 好酸球遊走因子に対するアラキドン酸過酸化物およびBSA脂質の影響(第38回大会研究発表要旨,日本ビタミン学会)
- 好酸球遊走因子・ペプチド性因子及びアラキドン酸過酸化物の活性 : 一般研究発表要旨
- 2-I-35 PAFの好酸球遊走活性(第41回大会一般研究発表)
- Amino Acids and Peptides. XX. : Inhibition of Papain by Succinyl-Gln-Val-Val-Ala-p-Nitroanilide, a Common Sequence of Endogenous Thiol Proteinase Inhibitors
- Amino Acids and Peptides. XIV. Synthesis and Biological Activity of Three S-Peptide Analogues of Bovine Pancreatic Ribonuclease A (RNase A)(Organic,Chemical)
- ペプチド合成研究45年の回顧
- Amino Acids and Peptides. XXIII. : Synthesis of N^α-Protected Amino Acid 6-Chloro-2-pyridyl Esters and Their Evaluation for Peptide Synthesis
- メタロチオネインの部分ペプチドに配位した109Cdの腎近位尿細管における部位選択的取り込みに関する検討