dc.identifier.uri |
http://dx.doi.org/10.15488/15517 |
|
dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/15638 |
|
dc.contributor.author |
Testolin, Giambattista
|
|
dc.contributor.author |
Richter, Jana
|
|
dc.contributor.author |
Ritter, Antje
|
|
dc.contributor.author |
Prochnow, Hans
|
|
dc.contributor.author |
Köhnke, Jesko
|
|
dc.contributor.author |
Brönstrup, Mark
|
|
dc.date.accessioned |
2023-11-24T05:59:41Z |
|
dc.date.available |
2023-11-24T05:59:41Z |
|
dc.date.issued |
2022 |
|
dc.identifier.citation |
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 |
|
dc.description.abstract |
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. |
eng |
dc.language.iso |
eng |
|
dc.publisher |
Weinheim : Wiley-VCH |
|
dc.relation.ispartofseries |
Chemistry - A European Journal 28 (2022), Nr. 54 |
|
dc.rights |
CC BY-NC 4.0 Unported |
|
dc.rights.uri |
https://creativecommons.org/licenses/by-nc/4.0 |
|
dc.subject |
antibiotics |
eng |
dc.subject |
antimicrobial resistance |
eng |
dc.subject |
natural products |
eng |
dc.subject |
oligoarylamides |
eng |
dc.subject |
photopharmacology |
eng |
dc.subject.ddc |
540 | Chemie
|
|
dc.subject.ddc |
660 | Technische Chemie
|
|
dc.title |
Optical Modulation of Antibiotic Resistance by Photoswitchable Cystobactamids |
eng |
dc.type |
Article |
|
dc.type |
Text |
|
dc.relation.essn |
1521-3765 |
|
dc.relation.issn |
0947-6539 |
|
dc.relation.doi |
https://doi.org/10.1002/chem.202201297 |
|
dc.bibliographicCitation.issue |
54 |
|
dc.bibliographicCitation.volume |
28 |
|
dc.bibliographicCitation.firstPage |
e202201297 |
|
dc.description.version |
publishedVersion |
|
tib.accessRights |
frei zug�nglich |
|