Semisynthetic Analogues of Anhydrotetracycline as Inhibitors of Tetracycline Destructase Enzymes
| Autor: | Chanez T. Symister, Hirdesh Kumar, Timothy A. Wencewicz, Luting Fang, Gautam Dantas, Niraj H. Tolia, Jana L. Markley, Andrew J. Gasparrini |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Tetracycline medicine.drug_class 030106 microbiology Tetracycline antibiotics medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound Omadacycline medicine Escherichia coli Enzyme Inhibitors chemistry.chemical_classification Escherichia coli Proteins Rational design Small molecule Anti-Bacterial Agents 030104 developmental biology Infectious Diseases Enzyme chemistry Biochemistry Tetracyclines Function (biology) medicine.drug |
| Popis: | The synthesis and biological evaluation of semisynthetic anhydrotetracycline analogues as small molecule inhibitors of tetracycline-inactivating enzymes are reported. Inhibitor potency was found to vary as a function of enzyme (major) and substrate-inhibitor pair (minor), and anhydrotetracycline analogue stability to enzymatic and nonenzymatic degradation in solution contributes to their ability to rescue tetracycline activity in whole cell Escherichia coli expressing tetracycline destructase enzymes. Taken collectively, these results provide the framework for the rational design of next-generation inhibitor libraries en route to a viable and proactive adjuvant approach to combat the enzymatic degradation of tetracycline antibiotics. |
| Databáze: | OpenAIRE |
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