Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action

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• 作者：Laurens H. J. Kleijn ; Sabine F. Oppedijk ; Peter ’t Hart ; Roel M. van Harten ; Leah A. Martin-Visscher ; Johan Kemmink ; Eefjan Breukink ; Nathaniel I. Martin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：April 14, 2016
• 年：2016
• 卷：59
• 期：7
• 页码：3569-3574
• 全文大小：331K
• 年卷期：0
• ISSN：1520-4804

文摘

Laspartomycin C is a lipopeptide antibiotic with activity against a range of Gram-positive bacteria including drug-resistant pathogens. We report the first total synthesis of laspartomycin C as well as a series of structural variants. Laspartomycin C was found to specifically bind undecaprenyl phosphate (C₅₅-P) and inhibit formation of the bacterial cell wall precursor lipid II. While several clinically used antibiotics target the lipid II pathway, there are no approved drugs that act on its C₅₅-P precursor.