Design and Synthesis of Peptide-Based Carboxylic Acid-Containing Transition-State Inhibitors of Human Neutrophil Elastase
| Autor: | Hiroshi Okazaki, Yasunao Inoue, Takemura Tadashi, Tomoki Omodani, Sato Fuminori, Komiya Masanobu, Kiyomi Imano |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lung Diseases
Carboxylic acid Clinical Biochemistry Carboxylic Acids Pharmaceutical Science Hemorrhage Peptide Tripeptide Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship In vivo Cricetinae Drug Discovery Animals Humans Amino Acids Enzyme Inhibitors Molecular Biology chemistry.chemical_classification biology Molecular Mimicry Organic Chemistry Elastase In vitro Enzyme chemistry Enzyme inhibitor Drug Design biology.protein Molecular Medicine Leukocyte Elastase Oligopeptides |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 12:551-555 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(01)00797-1 |
| Popis: | In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro inhibitory activity and also prevention of an undesirable toxicity. Of these, compound 9m has the most potent in vivo effect on HNE-induced lung hemorrhage in hamsters. |
| Databáze: | OpenAIRE |
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