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Extensive Structure-Activity Relationship Study of Albicidin's C-Terminal Dipeptidic p-Aminobenzoic Acid Moiety.
- Source :
-
Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2019 Dec 20; Vol. 25 (72), pp. 16538-16543. Date of Electronic Publication: 2019 Dec 11. - Publication Year :
- 2019
-
Abstract
- Albicidin is a recently described natural product that strongly inhibits bacterial DNA gyrase. The pronounced activity, particularly against Gram-negative bacteria, turns it into a promising lead structure for an antibacterial drug. Hence, structure-activity relationship studies are key for the in-depth understanding of structural features/moieties affecting gyrase inhibition, antibacterial activity and overcoming resistance. The 27 newly synthesized albicidins give profound insights into possibilities for variations of the C-terminus. Furthermore, in the present study, a novel derivative has been identified as overcoming resistance posed by the Klebsiella-protease AlbD. Structural modifications include, for example, azahistidine replacing the previous instable cyanoalanine as the central amino acid, as well as a triazole amide bond isostere between building blocks D and E.<br /> (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
Details
- Language :
- English
- ISSN :
- 1521-3765
- Volume :
- 25
- Issue :
- 72
- Database :
- MEDLINE
- Journal :
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 31642561
- Full Text :
- https://doi.org/10.1002/chem.201904752