Cover Picture: Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block (ChemMedChem 14/2016). (20th July 2016)

• Record Type: Journal Article
• Authors: Grätz, Stefan; Kerwat, Dennis; Kretz, Julian; von Eckardstein, Leonard; Semsary, Siamak; Seidel, Maria; Kunert, Maria; Weston, John B.; Süssmuth, R. D.
• Is Part Of: ChemMedChem. Volume 11:Number 14(2016)
• Page Start: 1483
• Page End: 1483
• Publication Date: 2016-07-20
• Subjects: albicidin -- antibiotics -- gyrase -- peptides -- structure–activity relationships; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600337
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The front cover picture shows the structure of albicidin, with modifications to the central amino acid. Albicidin, with its high activity against Gram‐negative as well as Gram‐positive bacterial strains, is a new lead structure to fulfil the strong demand for new antibiotics. The bullets in the revolver cylinder, namely Thr, Aib, Gly, Asp, and Lys represent the derivatives that were synthesized and tested. This set of amino acids allows charged as well as uncharged side chains to be introduced into the albicidin structure and, in addition, allows investigation of the influence of steric demand and chirality. The bacteria in the background are scared of the derivatives′ high potency, and somehow are not willing to accept this new nanomolar "weapon". In our study we could show that every tested derivative is even more potent than the parent albicidin, on its molecular target: namely DNA gyrase. Nevertheless, amino acids bearing charged side chains were less active in a cell‐based assay. Our studies on variations of the central building block of albicidin will therefore be helpful in the further optimization of this lead structure toward a future antibacterial drug. More information can be found in the Communication by Roderich Süssmuth et al. onpage 1499 in Issue 14, 2016 (DOI:10.1002/cmdc.201600163 ).