This paper describes the synthesis of 1,1-linked galactosyl mannosides as sialyl Lewis X mimetics that contain a spiro-ring to position the carboxylate group in a well-defined orientation. It was found that compound 4 is more active as a P-selectin inhibitor (IC50 = 19 microM) than the parent disaccharide 2, which contains a flexible carboxyl group (IC50 = 193 microM). This result is consistent with that observed in the previous NMR study of sialyl Lewis X bound to P-selectin. The chemistry described here should be useful for the development of selective inhibitors of E-, P-, and L-selectins. 相似文献
The reactions of various main-group metal hydrides with 1-halo-5-hexenes and with 1-halo-2,2-dlmethyl-5-hexenes produce both straight chain and cyclized reduction products. The formation of cyclic hydrocarbons clearly indicates the presence of radical intermediates during the course of these reactions. 相似文献
An ion trap mass spectrometer, equipped with a membrane/jet separator interface, is used for the direct detection of volatile and semi-volatile organic compounds in aqueous solutions. Aqueous sample is passed through a capillary membrane, the outside surface of which is continuously purged by helium. The permeate is pneumatically transported to the mass spectrometer via a jet separator which acts as an additional enrichment device. The performance and response characteristics of non-porous silicone and microporous polytetrafluoroethylene (PTFE) membranes are studied. The microporous membrane allows sufficient water to pass for it to be used as a reagent gas for chemical ionization. Both types of membranes provide detection limits in the parts per trillion (pptr) to parts per billion (ppb) range with a linear dynamic range of 3 orders of magnitude for some volatile organic compounds. Results show that there is no detectable matrix effect on response in the selected cases examined. The use of microporous membranes to analyze more polar compounds, such as 5-hydroxymethyl furfuraldehyde and lactic acid, is also demonstrated. The effects of other experimental parameters, such as membrane temperature and length, on sensitivity are also investigated. 相似文献
Pheophorbide a-induced photo-oxidation, in vitro, of cytochrome c oxidase and cytochrome c results in irreversible modifications to both protein components. Photo-oxidation of cytochrome c, as exhibited by change in its heme oxidation state, displays exponential kinetics and is detected with a lag period. Both the photo-induced inactivation of the enzyme, and destruction of the substrate ability of cytochrome c occur as complex multi-process events. Under similar experimental conditions, the loss of the substrate capability of cytochrome c develops approximately three times faster than inactivation of the enzyme. The slight lag in the photo-oxidation of cytochrome c is due to pheophorbide a-induced superoxide production. However, the relative amount of photo-oxidant produced is considerably more effective than the cytochrome c reducing capacity of the superoxide. Neither hydroxyl radical nor hydrogen peroxide are involved in the photo-oxidation of the heme function. The possibilities of heme oxidation by a singlet oxygen mediated pathway or direct electron abstraction involving the heme or apoprotein are not excluded. It is proposed that a multi-site oxidation of numerous reduced energy cofactors within cells may augment collateral enzyme inactivation in maximizing photosensitizer-induced cytotoxicity. Accordingly, amphipathic photosensitizers, capable of accessing both lipid and aqueous compartments containing reduced cofactors, may be more effective agents for photodynamic therapy than those which exhibit a high specificity of subcellular localization. 相似文献