Lantibiotics are believed to have a conceivable potential to be used as therapeutics, especially against clinically resistant bacterial strains. However, their low solubility and poor stability under physiological conditions limit their availability for clinical studies and further pharmaceutical commercialization. Nisin is a readily available and cheap lanthipeptide and thus serves as a good model in the search for the tools to engineer lantibiotics with improved pharmacological properties. This review aims to address technologies that can be applied to alter and enhance the antimicrobial activity, antibacterial spectrum and physicochemical properties (solubility, solution stability and protease resistance) of nisin. There are basically two general means to obtain nisin analogs—protein engineering and chemical functionalization of this antibiotic. Although bioengineering techniques have been well developed and enable the creation of nisin mutants of variable structures and properties, they are lacking spectacular effects so far. Chemical modifications of nisin based on utilization of the reactivity of its free amino and carboxylic moieties, as well as reactivity of the double bonds of its dehydroamino acids, are in their infancy.

We developed a simple and efficient method for the synthesis of functionalized unsymmetrical disulfanes under mild conditions in good yields. The designed method is based on the reaction of bis(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)disulfane with thiols in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The developed method allows the preparation of unsymmetrical disulfanes bearing additional hydroxy, carboxy, or amino functionalities.

We developed a simple and efficient method for the synthesis of functionalized unsymmetrical alkynyl sulfides under mild conditions in good yields.