Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 618-633 |
| Number of pages | 16 |
| Journal | ACS Infectious Diseases |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 12 2019 |
Keywords
- Tet(X)
- anhydrotetracycline
- antibiotic adjuvants
- antibiotic resistance
- enzymology
- eravacycline
- inactivating enzymes
- omadacycline
- tetracycline destructases
- tetracyclines
- tigecycline
Fingerprint Dive into the research topics of 'Semisynthetic analogues of anhydrotetracycline as inhibitors of tetracycline destructase enzymes'. Together they form a unique fingerprint.
Cite this
Markley, J. L., Fang, L., Gasparrini, A. J., Symister, C. T., Kumar, H., Tolia, N. H., Dantas, G., & Wencewicz, T. A. (2019). Semisynthetic analogues of anhydrotetracycline as inhibitors of tetracycline destructase enzymes. ACS Infectious Diseases, 5(4), 618-633. https://doi.org/10.1021/acsinfecdis.8b00349