Synthetic Lugdunin Analogues Reveal Essential Structural Motifs for Antimicrobial Action and Proton Translocation Capability

Abstract: Lugdunin, a novel thiazolidine cyclopeptide, exhibits micromolar activity against methicillin‐resistant Staphylococcus aureus (MRSA). For structure–activity relationship (SAR) studies, synthetic analogues obtained from alanine and stereo scanning as well as peptides with modified thiazolidine rings were tested for antimicrobial activity. The thiazolidine ring and the alternating d‐ and l‐amino acid backbone are essential. Notably, the non‐natural enantiomer displays equal activity, thus indicating the absence of a chiral target. The antibacterial activity strongly correlates with dissipation of the membrane potential in S. aureus. Lugdunin equalizes pH gradients in artificial membrane vesicles, thereby maintaining membrane integrity, which demonstrates that proton translocation is the mode of action (MoA). The incorporation of extra tryptophan or propargyl moieties further expands the diversity of this class of thiazolidine cyclopeptides.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Synthetic Lugdunin Analogues Reveal Essential Structural Motifs for Antimicrobial Action and Proton Translocation Capability ; volume:58 ; number:27 ; year:2019 ; pages:9234-9238 ; extent:5 ; Angewandte Chemie / International edition. International edition ; 58, Heft 27 (2019), 9234-9238 (gesamt 5)

Contributors, Places and Time

• Creator: Schilling, Nadine A. ; Berscheid, Anne ; Schumacher, Johannes ; Saur, Julian S. ; Konnerth, Martin C. ; Wirtz, Sebastian N. ; Beltrán‐Beleña, José M. ; Zipperer, Alexander ; Krismer, Bernhard ; Peschel, Andreas ; Kalbacher, Hubert ; Brötz, Heike ; Steinem, Claudia ; Grond, Stephanie

Further information

• DOI: 10.1002/anie.201901589
• URN: urn:nbn:de:101:1-2022071211124719125175
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:35 AM CEST