Antibacterial activity of the novel semisynthetic lantibiotic NVB333 in vitro and in experimental infection models.

NVB333 is a novel semisynthetic lantibiotic derived from the amide coupling of 3,5-dichlorobenzylamine to the C-terminal of deoxyactagardine B. The in vitro activity of NVB333 includes efficacy against clinically relevant pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. NVB333 shows no cross-resistance with other antibiotics tested and a very low propensity for resistance development.

Synthesis of peptides containing overlapping lanthionine bridges on the solid phase: an analogue of rings D and E of the lantibiotic nisin.

A methodology for the solid-phase synthesis of the overlapping lanthionine bridges found in many lantibiotics has been developed. A novel Teoc/TMSE-protected lanthionine derivative has been synthesized, and this lanthionine, and an Aloc/allyl-protected lanthionine derivative, have been incorporated into a linear peptide using solid-phase peptide synthesis. Selective deprotection of the silyl protecting groups, followed by sequential cyclization, deprotection of the allyl protecting groups, and further cyclization, enabled the regioselective formation of an analogue of rings D and E of nisin.

Crystal structures of Staphylococcusaureus methionine aminopeptidase complexed with keto heterocycle and aminoketone inhibitors reveal the formation of a tetrahedral intermediate.

High-resolution crystal structures of Staphylococcus aureus methionine aminopeptidase I in complex with various keto heterocycles and aminoketones were determined, and the intermolecular ligand interactions with the enzyme are reported. The compounds are effective inhibitors of the S. aureus enzyme because of the formation of an uncleavable tetrahedral intermediate upon binding.

The 1.15A crystal structure of the Staphylococcus aureus methionyl-aminopeptidase and complexes with triazole based inhibitors.

Methionyl aminopeptidases (MetAPs) represent a unique class of protease that are responsible for removing the N-terminal methionine residue from proteins and peptides. There are two major classes of MetAPs (type I and type II) described and each class can be subdivided into two subclasses. Eukaryotes contain both the type I and type II MetAPs, whereas prokaryotes possess only the type I enzyme.

A new route to sulfonamides via intermolecular radical addition to pentafluorophenyl vinylsulfonate and subsequent aminolysis.

[reaction: see text] Various radical species generated from either the corresponding iodo- or bromo- compounds and tri-n-butyltin hydride were added in an intermolecular fashion to the activated acceptor pentafluorophenyl vinylsulfonate. The products of each reaction were then subjected to aminolysis with a variety of different amines.

Solid-phase intermolecular radical reactions 2: synthesis of C-glycopeptide mimetics via a novel acrylate acceptor.

[reaction: see text] A novel tetrafluorophenol-linked acrylate is reported as an activated acceptor for intermolecular radical reactions. Addition of alkyl radicals led to pure products in good yields. We include here the first syntheses of C1- and C6-linked glycosides using a solid-phase radical methodology.