Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action
Publication date
2016-03-11
Authors
Kleijn, L.H.J.
Oppedijk, S.F.
't Hart, P.
van Harten, Roeland Maarten
Martin-Visscher, Leah A.
Kemmink, Johan
Breukink, Eefjan
Martin, Nathaniel
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Advisors
Supervisors
Document Type
Article
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taverne
Abstract
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.
Keywords
Taverne, Molecular Medicine, Drug Discovery
Citation
Kleijn, L H J, Oppedijk, S F, T Hart, P, van Harten, R, Martin-Visscher, L A, Kemmink, J, Breukink, E & Martin, N I 2016, 'Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action', Journal of Medicinal Chemistry, vol. 59, no. 7, pp. 3569-3574. https://doi.org/10.1021/acs.jmedchem.6b00219