NMR Shows Why a Small Chemical Change Almost Abolishes the Antimicrobial Activity of Glycocin F.

Glycocin F (GccF), a ribosomally synthesized, post-translationally modified peptide secreted by KW30, rapidly inhibits the growth of susceptible bacteria at nanomolar concentrations. Previous studies have highlighted structural features important for its activity and have shown the absolute requirement for the Ser18 -linked GlcNAc on the eight-residue loop linking the two short helices of the (C-X6-C) structure. Here, we show that an ostensibly very small chemical modification to Ser18, the substitution of the C proton with a methyl group, reduces the antimicrobial activity of GccF 1000-fold (IC 1.

Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.

Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria. Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions. It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.

Using Chemical Synthesis to Probe Structure-Activity Relationships of the Glycoactive Bacteriocin Glycocin F.

Glycocin F, a bacteriocin produced by Lactobacillus plantarum KW30, is glycosylated with two N-acetyl-d-glucosamine sugars, and has been shown to exhibit a rapid and reversible bacteriostasis on susceptible cells. The roles of certain structural features of glycocin F have not been studied to date. We report here the synthesis of various glycocin F analogues through solid-phase peptide synthesis (SPPS) and native chemical ligation (NCL), allowing us to probe the roles of different structural features of this peptide.

Total chemical synthesis of glycocin F and analogues: -glycosylation confers improved antimicrobial activity.

Glycocin F (GccF) is a unique diglycosylated bacteriocin peptide that possesses potent and reversible bacteriostatic activity against a range of Gram-positive bacteria. GccF is a rare example of a 'glycoactive' bacteriocin, with both the -linked -acetylglucosamine (GlcNAc) and the unusual -linked GlcNAc moiety important for antibacterial activity. In this report, glycocin F was successfully prepared using a native chemical ligation strategy and folded into its native structure.

Postcomplexation synthetic routes to dipyrrin complexes.

We report a postfunctionalization synthetic route to dipyrrin complexes that gives access to a broad range of new complexes. This route involves the coordination of a 5-methylthiodipyrrinato ligand to a metal centre followed by displacement of the thiomethyl moiety by a nucleophile. Using rhenium(I) as a platform and amine nucleophiles, we show how complexes that would be difficult or impossible to synthesize via traditional methods can now be accessed.