Conformationally Constrained Analogues of Diacylglycerol. 18. The Incorporation of a Hydroxamate Moiety into Diacylglycerol-Lactones Reduces Lipophilicity and Helps Discriminate between sn-1 and sn-2 Binding Modes to Protein Kinase C (PK-C). Implications for Isozyme Specificity
| Autor: | Larry L. Pearce, Kee-Chung Han, Jeewoo Lee, Shunqi Yan, Ji-Hye Kang, Marc C. Nicklaus, Samira Benzaria, Peter M. Blumberg, Victor E. Marquez, Nancy E. Lewin |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Molecular Conformation Hydroxamic Acids Ligands Diglycerides Lactones Structure-Activity Relationship chemistry.chemical_compound 4-Butyrolactone Amide Drug Discovery Moiety Protein Kinase C Protein kinase C Diacylglycerol kinase chemistry.chemical_classification Hydroxamic acid Chemistry Isoenzymes Drug Design Lipophilicity Molecular Medicine lipids (amino acids peptides and proteins) Lactone Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry. 44:4309-4312 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | An approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date. |
| Databáze: | OpenAIRE |
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