Effect of the structure of adenosine mimic of bisubstrate-analog inhibitors on their activity towards basophilic protein kinases
| Autor: | Mart Roben, Asko Uri, Gerda Raidaru, Marie Kriisa, Grete Kadak, Erki Enkvist |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adenosine
Clinical Biochemistry Pharmaceutical Science Peptide Thiophenes Arginine Biochemistry Drug Discovery medicine Binding site Protein kinase A Protein Kinase Inhibitors Molecular Biology chemistry.chemical_classification rho-Associated Kinases Binding Sites biology Kinase Organic Chemistry Cyclic AMP-Dependent Protein Kinases Basophilic Pyrimidines Enzyme chemistry Enzyme inhibitor biology.protein Molecular Medicine Peptides Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:6098-6101 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.09.026 |
| Popis: | Previously reported structural fragments that associate with the ATP-binding pocket of basophilic protein kinases were conjugated with d-arginine-containing peptides. Inhibitory potency of the resulting bisubstrate-analog inhibitors towards PKA and ROCK-II extended to subnanomolar range. The conjugates incorporating 2-pyrimidyl-5-amidothiophene fragment had the highest activity and at 100 nM concentration exhibited over 80% inhibition of most of the tested basophilic kinases of the AGC group. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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