Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry
| Autor: | Meggin Taylor, Robert Lowell Simmons, Amy D. Fung, Daniel A. Erlanson, Mark T. Cancilla, Nina Viswanathan, Molly M. He, Kathy Cao |
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| Rok vydání: | 2008 |
| Předmět: |
Stereochemistry
Chemistry Pharmaceutical Clinical Biochemistry Fragment-based lead discovery Aurora inhibitor Pharmaceutical Science Computational biology Protein Serine-Threonine Kinases Crystallography X-Ray Ligands Biochemistry Mass Spectrometry Structure-Activity Relationship Aurora Kinases Drug Discovery Dynamic combinatorial chemistry Transferase Structure–activity relationship Combinatorial Chemistry Techniques Binding site Enzyme Inhibitors Molecular Biology Binding Sites Molecular Structure Ligand Chemistry Organic Chemistry Models Chemical Purines Drug Design Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 18(14) |
| ISSN: | 1464-3405 |
| Popis: | We demonstrate a fragment-based lead discovery method that combines site-directed ligand discovery with dynamic combinatorial chemistry. Our technique targets dynamic combinatorial screening to a specified region of a protein by using reversible disulfide chemistry. We have used this technology to rapidly identify inhibitors of the drug target Aurora A that span the purine-binding site and the adaptive pocket of the kinase. The binding mode of a noncovalent inhibitor has been further characterized through crystallography. |
| Databáze: | OpenAIRE |
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