Tridecaptin A 1 (TriA 1 ) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA 1 exerts its bactericidal effect by binding to the bacterial cellwall 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 TriA 1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA 1 -lipid II complex. These results suggest that TriA 1 kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.antibiotic | peptide | lipid II | peptidoglycan | membrane pore

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.

Due to the wide importance of β-phosphorylated ketones as key building-blocks in the fabrication of various pharmaceutically active organophosphorus compounds, finding new and truly efficient methods for their preparation.

A catalytic method for the synthesis of a class of hydrazine derivatives is reported. The described method provides convenient access to compounds which are anticipated to show biological activities. The salient features of this process include operational simplicity, good yields, and easily accessible starting materials.