Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C
| Autor: | Takeshi Yanagisawa, Satoshi Mayumi, Yoshiyasu Baba, Go Hirai, Kumiko Nagamatsu, Mikiko Sodeoka, Yuichi Hashimoto, Yosuke Ogoshi |
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| Rok vydání: | 2004 |
| Předmět: |
Molecular model
Stereochemistry Clinical Biochemistry Pharmaceutical Science Ligands Biochemistry Structure-Activity Relationship Drug Discovery Structure–activity relationship Humans Binding site Enzyme Inhibitors Molecular Biology Protein kinase C Protein Kinase C Benzofurans chemistry.chemical_classification Binding Sites Dose-Response Relationship Drug Molecular Structure Ligand Organic Chemistry Hydrogen Bonding General Medicine Ligand (biochemistry) Intracellular signal transduction Enzyme Design synthesis chemistry Drug Design Molecular Medicine Signal transduction Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 14(11) |
| ISSN: | 0960-894X |
| Popis: | Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. We have designed novel PKC ligands having an isobenzofuranone template, based on the proposed interaction of DAG (1,2-diacyl-sn-glycerol) with the PKCdelta C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCalpha binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCalpha ligand, and the structure-activity relationship is well explained by our proposed binding model. |
| Databáze: | OpenAIRE |
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