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Lantibiotics, a group of lanthionine-containing peptides, display their antibiotic activity by combining different killing mechanisms within one molecule. The prototype lantibiotic nisin was shown to possess both inhibition of peptidoglycan synthesis and pore formation in bacterial membranes by interacting with lipid II. Gallidermin, which shares the lipid II binding motif with nisin but has a shorter molecular length, differed from nisin in pore formation in several strains of bacteria. To simulate the mode of action, we applied cyclic voltammetry and quartz crystal microbalance to correlate pore formation with lipid II binding kinetics of gallidermin in model membranes. The inability of gallidermin to form pores in DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) (C18/1) and DPoPC (1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine) (C16/1) membranes was related to the membrane thickness. For a better simulation of bacterial membrane characteristics, two different phospholipids with branched fatty acids were incorporated into the DPoPC matrix. Phospholipids with methyl branches in the middle of the fatty acid chains favored a lipid II-independent DPoPC permeabilization by gallidermin, while long-branched phospholipids in which the branch is placed near the hydrophilic region induced an identical lipid II-dependent pore formation of gallidermin and nisin. Obviously, the branched lipids altered lipid packing and reduced the membrane thickness. Therefore, the duality of gallidermin activity (pore formation and inhibition of the cell wall synthesis) seems to be balanced by the bacterial membrane composition.

Drug-induced agranulocytosis is a life-threatening side effect that usually manifests as a severe form of neutropenia associated with fever or signs of sepsis. It can occur as a problem in the context of therapy with a wide variety of drug classes. Numerous drugs are capable of triggering the rare idiosyncratic form of agranulocytosis, which, unlike agranulocytosis induced by cytotoxic drugs in cancer chemotherapy, is characterised by “bizzare” type B or hypersensitivity reactions, poor predictability and a mainly low incidence. The idiosyncratic reactions are thought to be initiated by chemically reactive drugs or reactive metabolites that react with proteins and may subsequently elicit an immune response, particularly directed against neutrophils and their precursors. Cells or organs that exhibit specific metabolic and biotransformation activity are therefore frequently affected. In this review, we provide an update on the understanding of drug-induced idiosyncratic agranulocytosis. Using important triggering drugs as examples, we will summarise and discuss the chemical, the biotransformation-related, the mechanistic and the therapeutic basis of this clinically relevant and undesirable side effect.

Stereoselective synthesis of glycosides (glucosides, galactosides, mannosides, and xylosides) is reported using long-chain alcohols with 0-4 ethoxy spacers as potential anchored cryoprotectors.Glycolipids are one of the basic constituents of biological membranes besides phospholipids. The sugar residues in these membranes on the cell surface are playing an important role in the biological response. With this goal we have tried to analyze the influence of different sugar units on the physicochemical properties of phospholipid systems, especially hydration"] and the behavior of lipid systems during water removal under freezing condition and desiccation (lyophilization)[21 and also on the interaction between phospholipidglycolipid systems with cells131. Glycosides of long- R'OR chain alcohols are of our special interest because of the homogeneity of their mixture with phosphatidyl choline to an unlimited extent, also resulting to the formation of lipid vesicles in these mixturesr41. For these investigations we required some glycosides of different sugars with long-chain alkyl groups and with spacers containing a different number of ethyleneoxy groups between sugar and alkyl moiety.Although a number of methods [5] are known in the literature for glycosidation, none of the three existing main methods, namely the Koenigs-Knorr method, the Lewis acidcatalyzed process and the synthesis using a phase-transfer catalyst (PTC) provides good stereoselectivity in good overall yield, particularly with long-chain alcohols because of their low reactivity. Especially cis glycosidation is still prob-

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