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Cover Feature: Cystobactamid 507: Concise Synthesis, Mode of Action, and Optimization toward More Potent Antibiotics (Chem. Eur. J. 32/2020)
Author(s) -
Elgaher Walid A. M.,
Hamed Mostafa M.,
Baumann Sascha,
Herrmann Jennifer,
Siebenbürger Lorenz,
Krull Jana,
Cirnski Katarina,
Kirschning Andreas,
Brönstrup Mark,
Müller Rolf,
Hartmann Rolf W.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002127
Subject(s) - dna gyrase , topoisomerase , intercalation (chemistry) , chemistry , dna , mode of action , stereochemistry , intramolecular force , hydrogen bond , antibiotics , mechanism of action , antibacterial activity , combinatorial chemistry , biophysics , biochemistry , bacteria , biology , escherichia coli , genetics , molecule , in vitro , organic chemistry , gene
Optimization of the natural antibiotic cystobactamid 507 targeting DNA gyrase and topoisomerase IV was attained by structure– and conformation—activity relationship studies. The bioactive conformation was recognized as syn using conformationally locked analogues via intramolecular hydrogen bonds. The new compounds displayed improved target inhibition, antibacterial activity, stability to metabolism and the resistance factor AlbD. Mode of action study revealed that cystobactamids bind to the DNA part of the gyrase–DNA complex at the minor groove with no intercalation. More information can be found in the Full Paper by R. W. Hartmann et al. on page 7219.