Design, synthesis, and characterization of an ATP-peptide conjugate inhibitor of protein kinase A
| Autor: | Aliya C. Hines, Philip A. Cole |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Mitogen-activated protein kinase kinase Protein Serine-Threonine Kinases Biochemistry Binding Competitive MAP2K7 Structure-Activity Relationship Adenosine Triphosphate Drug Discovery c-Raf Enzyme Inhibitors Molecular Biology Protein kinase C Serine/threonine-specific protein kinase MAP kinase kinase kinase Chemistry Organic Chemistry Receptor protein serine/threonine kinase Cyclic AMP-Dependent Protein Kinases Kinetics Drug Design Molecular Medicine Cyclin-dependent kinase 9 Oligopeptides |
| Zdroj: | Bioorganicmedicinal chemistry letters. 14(11) |
| ISSN: | 0960-894X |
| Popis: | An ATP-peptide conjugate was synthesized as a bisubstrate analogue inhibitor of the serine/threonine kinase protein kinase A. The compound was found to be a linear, competitive inhibitor with respect to ATP substrate, exhibiting a Ki of 3.8 μM. The compound was noncompetitive with respect to peptide substrate. The inhibitor was shown to be selective for protein kinase A versus the closely related protein kinase C as well as tyrosine kinase Csk. This analysis provides new evidence for the dissociative transition state of protein serine/threonine kinases and illustrates a simple method to convert a low affinity peptide substrate to a selective and moderately potent inhibitor for these enzymes. |
| Databáze: | OpenAIRE |
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