We developed a new cationic lipid suitable for use as a DNA carrier in the presence of 10% sera. The novel compound (abbreviated as Arg-Chol) contains cholesterol and a dipeptide consisting of glycine and sterically protected arginine. The efficiency of reporter gene transfection using liposomes based on this new reagent was compared with that of liposomes made with other cationic derivatives of cholesterol. Lipoplexes formulated with the newly synthesized lipid mediate in vitro transfection of B16(F10) murine melanoma cells in the presence of 10% sera more efficiently than in other cell lines and compared with other cholesterol derivatives studied.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Disulfiram (CAS 97-77-8, DSF), a potent anticarcinogenic compound, is known to form mixed disulfides with sulfhydryl group containing amino acids or proteins in vivo. In the present study the stabilities of two mixed disulfides which may arise in the metabolism of disulfiram, i.e. S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) and S-(N,N-diethyldithiocarbamoyl)-L-glutathione (GS-DDTC) in phosphate buffer (pH 7.2) and in rat liver subcellular fractions were investigated as well as their influences on the glutathione (GSH)-related detoxifying system, on the metabolism of [14C] N-nitrosodiethylamine (NDEA) and on the genotoxic activity of NDEA in rats. Both substances were stable in buffer and in microsomes but were degraded in cytosol showing a half life of 4.7 h (AC-DDTC) and 3.2 h (GS-DDTC). Addition of GSH to the incubation media accelerated the degradation of mixed disulfides in cytosol. In vivo administration of AC-DDTC and GS-DDTC (1.7 mmol/kg i.p.) led to an increase in hepatic GSH content and to an inhibition of the activity of NDEA deethylase. Both mixed disulfides inhibited the metabolism of NDEA. After a 28 mg/kg i.p. dose of [14C] NDEA only 0.4% was excreted unchanged in the urine. Pretreatment with AC-DDTC and GS-DDTC caused a 10 to 20 fold increase in the amount of NDEA excreted in the urine. The occurrence of DNA single strand breaks in rat liver cells induced by NDEA was completely neutralized by the pretreatment with AC-DDTC.

N-Fmoc-3-O-Tr-l-serine methyl and benzyl esters, as well as a tripeptide FmocAlaSer(Tr)GlyOBn were directly glycosylated by 3,4,6-tri-O-acetyl-1,2-O-(1-cyanoethylidene)-α-d-galactopyranose in the presence of TrClO4 in dichloromethane, yielding 32–57% of N-Fmoc-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-l-serine esters and the corresponding tripeptide.

It is generally assumed that thiol anticarcinogens like disulfiram (DSF) or sodium 2-mercaptoethane-sulfonate (mesna) after in vivo administration react rapidly with serum protein sulfhydryl groups forming mixed disulfides. Different methods have been established for the synthesis of mixed disulfides between cysteine or glutathione and diethyldithiocarbamate (DDTC) or mesna in order to elucidate their chemical and biological effects. A short summary is given of pilot biochemical experiments carried out with two mixed disulfides.

Polystyrene sodium sulfinate reacted with thionitrites gave polystyrene thiolsulfonates. These immobilised thioalkylation reagents were used for an effective synthesis of mixed disulfides.