Immobilization of a Novel Antibacterial Agent on Solid Phase and Subsequent Isolation of EF-Tu
| Autor: | Anthony W. Yem, W. Rodney Mathews, Atli Thorarensen, Michael John Bohanon, Michael T. Sweeney, Timothy P. Boyle, Cindy L Wolfe, Charlotte L. Heckaman, Keith R. Marotti, Martin R. Deibel, Alice L. Bodnar, Gary E. Zurenko |
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| Rok vydání: | 2004 |
| Předmět: |
Staphylococcus aureus
Stereochemistry Biomedical Engineering Pharmaceutical Science Bioengineering Plasma protein binding Peptide Elongation Factor Tu Chromatography Affinity Drug Delivery Systems Phase (matter) medicine Chromatography High Pressure Liquid Antibacterial agent Pharmacology Chemistry Organic Chemistry Combinatorial chemistry Anti-Bacterial Agents Thiazoles Pyrimidines Metabolic labeling Mechanism of action Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization medicine.symptom Linker EF-Tu Protein Binding Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 15:333-343 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | Screening of our compound collection identified PNU-92560, a 2-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carboxamide, as a novel antibacterial agent. Extensive analogue development identified that the 2-position of the thiadiazole could be functionalized with a linker that would allow the compound to be attached to a solid support. The extreme insolubility of the analogues prevented the mechanism of action for these compounds to be determined utilizing traditional methodology. The solid-supported compounds were utilized as affinity columns to identify elongation factor Tu (EF-Tu) as a putative target for this class of compounds. The activity of the compounds in a metabolic labeling experiments and in translation assay supports the identity of the target for these compounds to be EF-Tu. |
| Databáze: | OpenAIRE |
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