Testolin, G.; Richter, J.; Ritter, A.; Prochnow, H.; Köhnke, J. et al.: Optical Modulation of Antibiotic Resistance by Photoswitchable Cystobactamids. In: Chemistry - A European Journal 28 (2022), Nr. 54, e202201297. DOI: https://doi.org/10.1002/chem.202201297
Zusammenfassung: | |
The rise of antibiotic resistance causes a serious health care problem, and its counterfeit demands novel, innovative concepts. The combination of photopharmacology, enabling a light-controlled reversible modulation of drug activity, with antibiotic drug design has led to first photoswitchable antibiotic compounds derived from established scaffolds. In this study, we converted cystobactamids, gyrase-inhibiting natural products with an oligoaryl scaffold and highly potent antibacterial activities, into photoswitchable agents by inserting azobenzene in the N-terminal part and/or an acylhydrazone moiety near the C-terminus, yielding twenty analogs that contain mono- as well as double-switches. Antibiotic and gyrase inhibition properties could be modulated 3.4-fold and 5-fold by light, respectively. Notably, the sensitivity of photoswitchable cystobactamids towards two known resistance factors, the peptidase AlbD and the scavenger protein AlbA, was light-dependent. While irradiation of an analog with an N-terminal azobenzene with 365 nm light led to less degradation by AlbD, the AlbA-mediated inactivation was induced. This provides a proof-of-principle that resistance towards photoswitchable antibiotics can be optically controlled. | |
Lizenzbestimmungen: | CC BY-NC 4.0 Unported |
Publikationstyp: | Article |
Publikationsstatus: | publishedVersion |
Erstveröffentlichung: | 2022 |
Die Publikation erscheint in Sammlung(en): | Forschungszentren |
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