[en] Published in summary form only

[en] Published in summary form only

[en] Fast atom bombardment mass spectrometry combined with various tandem mass spectrometric techniques and accurate mass measurement were used to elucidate the structure of an unknown biologically active peptide isolated from Locusa migratoria. (author). 23 refs.; 6 figs.; 2 schemes

[en] A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting compounds of this series was N-glycyl-S-acetylcysteamine trifluoroacetate (16, I 102). Structure-activity relationships are discussed

[en] Abstract only. 5 refs

[en] Reactivities of two epoxy substrate homologs in the reaction catalyzed by some prenyltransferases were examined from both synthetic and mechanistic view points. Two substrate homologs, 6,7-epoxygeranyl diphosphate (1) and 6,7-epoxybishomogeranyl diphosphate (2), were chemically synthesized. Farnesyl diphosphate synthase prepared from pig liver and Micrococcus luteus respectively, were used. After the epoxy compounds were incubated with [1-¹⁴C] isopentenyl diphosphate and enzyme, the products were extracted with butanol. The reactivities of the epoxy compounds were estimated by the radioactivity in the extracts. Both 1 and 2 were active as substrates for SPP synthase and FPP synthase, and they showed optimal reactivities at much higher concentrations than the natural substrates. Structural determination of the epoxide incorporated, will be presented as well as some new aspects of the prenyltransferase mechanism

[en] Short communication

[en] A definite angular dependence of shallow dose from energetic electrons was observed when measuring the angular response of several detectors. This angular dependence of dose appeared to be fundamental, not a detector artifact. The theoretical response of a detector is discussed and compared to measurements of shallow dose with tissue and phantom response detectors. The energy-dependent angular response of the dose observed could not be explained by simple trigonometric arguments. The response, which is backscatter-dependent, must be considered in detector design and dose measurements. It is not possible for standard detectors to follow this response

[en] A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested

[en] The nitroimidazole-linked phenanthridine series of compounds (NLP-1, 2, and 3) were synthesized under the assumption that it should be possible to enhance the molar efficiency of 2-nitroimidazoles as hypoxic cell radiosensitizers and cytotoxins by targeting them to their likely site of action, DNA. The targeting group chosen was the phenanthridine moiety, the major component of the classical DNA intercalating compound, ethidium bromide. The sole difference between the compounds is the length of the hydrocarbon chain linking the nitroimidazole to the phenanthridine. The phenanthridine group with a three-carbon side chain, P-1, was also synthesized to allow studies on the effect of the targeting group by itself. The ability of the compounds to bind to DNA is inversely proportional to their linker chain length with binding constant values ranging from approximately 1 x 10(5) mol-1 for NLP-2 to 6 x 10(5) mol-1 for NLP-3. The NLP compounds show selective toxicity to hypoxic cells at 37 degrees C at external drug concentrations 10-40 times lower than would be required for untargeted 2-nitroimidazoles such as misonidazole in vitro. Toxicity to both hypoxic and aerobic cells is dependent on the linker chain: the shorter the chain, the greater the toxicity. In addition, the NLP compounds radiosensitize hypoxic cells at external drug concentrations as low as 0.05 mM with almost the full oxygen effect being observed at a concentration of 0.5 mM. These concentrations are 10-100 times lower than would be required for similar radiosensitization using misonidazole. Radiosensitizing ability is independent of linker chain length. The present compounds represent prototypes for further studies of the efficacy and mechanism of action of 2-nitroimidazoles targeted to DNA by linkage to an intercalating group