Adenosine analogue inhibitors of S-adenosylhomocysteine hydrolase
| Autor: | Carrie Wolffe, Mark E. Fraley, Alexander Mccampbell, Rebecca B. White, Rena Zhang, John Majercak, Mary J. Savage, William J. Ray, Sang Jin Na, George D. Hartman, Shaei Y. Huang, Timothy J. Hartingh, Antonella Converso, Robert M. Garbaccio, Yuanjiang Yu, Suzie Yeh |
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| Rok vydání: | 2014 |
| Předmět: |
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Molecular Adenosine Homocysteine Hydrolases Clinical Biochemistry Pharmaceutical Science Biochemistry Substrate Specificity Inhibitory Concentration 50 chemistry.chemical_compound Enzyme activator In vivo Drug Discovery Hydrolase medicine Animals Enzyme Inhibitors Molecular Biology Brain Chemistry chemistry.chemical_classification Organic Chemistry Hydrogen Bonding S-Adenosylhomocysteine In vitro Rats Enzyme Activation Cytosol Enzyme chemistry Drug Design Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:2737-2740 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2014.04.034 |
| Popis: | Elevated plasma homocysteine (Hcy) levels are an independent risk factor for the onset and progression of Alzheimer's disease. Reduction of Hcy to normal levels therefore presents a new approach for disease modification. Hcy is produced by the cytosolic enzyme S-adenosylhomocysteine hydrolase (AHCY), which converts S-adenosylhomocysteine (SAH) to Hcy and adenosine. Herein we describe the design and characterization of novel, substrate-based S-adenosylhomocysteine hydrolase inhibitors with low nanomolar potency in vitro and robust activity in vivo. |
| Databáze: | OpenAIRE |
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