MRSA Research Today is a free monthly online journal that collates and summarizes the latest research about MRSA, including details on methicillin-resistant staphylococcus aureus, hospitals, infection, antibiotic resistance, superbugs.

Total synthesis of lysobactin.

Guzman-Martinez A, Lamer R, VanNieuwenhze MS

Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.

Antibiotic resistance has become a significant public health concern. Antibiotics that belong to new structural classes and manifest their biological activity via novel mechanisms are urgently needed. Lysobactin, a depsipeptide antibiotic has displayed very strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as vancomycin-resistant enterococci (VRE) with minimum inhibitory concentrations (MICs) ranging from 0.39 to 0.78 microg/mL. The MIC values against VRE were more than 50-fold lower than those reported for vancomycin itself. Lysobactin was found to inhibit nascent peptidoglycan formation; however, this activity was not antagonized in the presence of N-acyl-L-Lys-D-Ala-D-Ala, the binding domain on the cell wall precursors that is utilized by vancomycin. Thus, lysobactin represents a promising agent for the treatment bacterial infections due to resistant pathogens. We describe a convergent synthesis of lysobactin that relies upon a highly efficient macrocyclization reaction to assemble the 28-membered cyclic depsipeptide. This synthesis provides the foundation for further study of the mode of action utilized by lysobactin and its analogues.

Published 2 May 2007 in J Am Chem Soc, 129(18): 6017-21.
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