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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / pharmacology*
-
Cell Wall / drug effects*
-
Lipopeptides / chemical synthesis*
-
Lipopeptides / pharmacology*
-
Microbial Sensitivity Tests
-
Peptides, Cyclic / chemical synthesis*
-
Peptides, Cyclic / pharmacology*
-
Staphylococcus aureus / drug effects*
-
Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives
-
Uridine Diphosphate N-Acetylmuramic Acid / antagonists & inhibitors
Substances
-
Anti-Bacterial Agents
-
Lipopeptides
-
Peptides, Cyclic
-
Uridine Diphosphate N-Acetylmuramic Acid
-
laspartomycin C
-
muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol