Recent trends in the direct oxyphosphorylation of C-C multiple bonds.

Due to the wide importance of ß-phosphorylated ketones as key building-blocks in the fabrication of various pharmaceutically active organophosphorus compounds, finding new and truly efficient methods for their preparation from simple, low-cost and ubiquitous feedstock materials within a single click is an interesting subject in organic synthesis. Recently, oxyfunctionalization of carbon-carbon multiple bonds has arisen as a straightforward and versatile tool for the synthesis of complex organic molecules from the simple and easily accessible alkenes/alkynes via a single operation. In this context, oxyphosphorylation of alkenes/alkynes with P(O)-H compounds has attracted considerable attention as a unique procedure for the construction of ß-phosphorylated ketones. In this review, we outline the recent advances and developments in this fast-growing research field with particular emphasis on the mechanistic aspects of reaction.

Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147.

Lacticin 3147 is a two peptide lantibiotc (LtnA1 and LtnA2) that displays nanomolar activity against many Gram-positive bacteria. Lacticin 3147 may exert its antimicrobial effect by several mechanisms. Isothermal titration calorimetry experiments show that only LtnA1 binds to the peptidoglycan precursor lipid II, which could inhibit peptidoglycan biosynthesis. An experimentally supported model of the resulting complex suggests that the key binding partners are the C-terminus of LtnA1 and pyrophosphate of lipid II. A combination of in vivo and in vitro assays indicates that LtnA1 and LtnA2 can induce rapid membrane lysis without the need for lipid II binding. However, the presence of lipid II substantially increases the activity of lacticin 3147. Furthermore, studies with synthetic LtnA2 analogues containing either desmethyl- or oxa-lanthionine rings confirm that the precise geometry of these rings is essential for this synergistic activity.

Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II.

Tridecaptin A1 (TriA1) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA1 exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA1-lipid II complex. These results suggest that TriA1 kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.