期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 27, 页码 9234-9238出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201901589
关键词
aldehyde peptide synthesis; methicillin-resistant Staphylococcus aureus; proton translocation; synthetic membrane vesicles; thiazolidine antibiotics
资金
- Institutional Strategy of the University of Tubingen (DFG) [ZUK 63]
- Cluster of Excellence [EXC 2124]
- DZIF
- [RTG 1708]
- [SFB 766]
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.
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