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

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.

New Insights into Nisin's Antibacterial Mechanism Revealed by Binding Studies with Synthetic Lipid II Analogues.

Nisin is the preeminent lantibiotic, and to date its antibacterial mechanism has been investigated using a variety of techniques. While nisin's lipid II-mediated mode of action is well-established, a detailed analysis of the thermodynamic parameters governing this interaction has not been previously reported. We here describe an approach employing isothermal titration calorimetry to directly measure the affinity of nisin for lipid II and a number of synthetic lipid II precursors and analogues.

Hit 'em where it hurts: The growing and structurally diverse family of peptides that target lipid-II.

Understanding the mode of action of antibiotics is becoming more and more important in the time that microorganisms start to develop resistance. One very well validated target of several classes of antibiotics is the peptidoglycan precursor lipid II. In this review different classes of lipid II targeting antibiotics will be discussed in detail, including the lantibiotics, human invertebrate defensins and the recently discovered teixobactin.

A combined solid- and solution-phase approach provides convenient access to analogues of the calcium-dependent lipopeptide antibiotics.

The calcium-dependent lipopeptide antibiotics represent a promising new class of antimicrobials for use in combating drug-resistant bacteria. At present, daptomycin is the only such lipopeptide used clinically and displays potent antimicrobial activity against a number of pathogenic Gram-positive bacteria. Given the increasing need for new antibiotics, practical synthetic access to unnatural analogues of daptomycin and related antimicrobial lipopeptides is of value.