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991.
The structure of the title compound displays a buckled diketopiperazine ring. The two side-chains are both folded, with the imidazole ring facing the methionine chain. Imidazole nitrogen is the primary site for metal coordination of the ligand. Only for copper (II) adducts and in the solid state are there evidences of additional coordination through the sulfur atom. 相似文献
992.
ENEA MENEGATTI SANTO SCALIA FABRIZIO BORTOLOTTI PAOLO ASCENZI ANTONIO DE MARCO 《Chemical biology & drug design》1989,34(3):161-165
Tryptic digestion of the mouse epidermal growth factor (mEGF) and the chromatographic separation of its proteolytic fragments by RP-HPLC affords the isolation of the pure hormone, of its 1–48 (Des(49–53)mEGF) and 1–45 (Des(46–53)mEGF) derivatives, and of the carboxyl-terminal pentapeptide W49–W50-E51-L52-R53. Kinetics of mEGF proteolytic degradation follows a two-state time-course: native mEGF being converted into Des(49–53)mEGF with an apparent half-time of 10min; and Des(49–53)mEGF subsequently hydrolyzed to Des(46–53)mEGF with an apparent half-time of 7 h. Native mEGF and its proteolytic fragments have been characterized by 1H-n.m.r. spectroscopy. In the aromatic and aliphatic regions, the 1H-n.m.r. spectrum proved to be a sufficiently sensitive probe for following controlled proteolysis, and for analyzing the influence of the carboxyl-terminal sequence on the hormone conformation and stability. 相似文献
993.
Summary The ribosomal proteins of two ascomycetes Podospora anserina and Saccharomyces cerevisiae, were compared by two dimensional electrophoresis in two different gel systems and we found only five pairs of proteins which have kept homologous physico-chemical properties under these conditions. An immunological analysis was performed by radioimmunodetection of proteins blotted on nitrocellulose sheet after separation by electrophoresis, with four sera directed against the r-proteins of each subunit of these fungi. So, we pointed out many common antigenic sites present on proteins which do not co-migrate except for yeast L3 and L1 of P. anserina which have the same properties. 相似文献
994.
Summary Islets from diabetic C57BL/KsJ db/db mice and normal C57BL/KsJ +/+ mice were loaded with 86Rb+ and micro-perifused with nonradioactive medium for 25 min. The appearance of 86Rb+ in the effluent could be described as the sum of two exponential functions with different proportionality constants. The rapid efflux component may have represented washout from the extracellular space, and had about the same proportionality constant in normal and diabetic mice. The slow efflux component probably reflected efflux across the islet cell plasma membranes. At 3 mmol/l D-glucose in the medium, the slow efflux was significantly retarded in diabetic as compared with normal mice. In normal mice, but not in diabetics, 20 mmol/l D-glucose inhibited the slow efflux component. It is concluded that the basal K+ permeability is decreased in KsJ db/db mouse islet cells, and that this abnormality may explain their persistant depolarization at low glucose concentrations. 相似文献
995.
E.R. STIMSON Y.C. MEINWALD G.T. MONTELIONE H.A. SCHERAGA 《Chemical biology & drug design》1986,27(6):569-582
Vicinal coupling constants between various nuclei provide backbone and side-chain conformational information for a series of asparagine- and tyrosine-containing peptides in DMSO and in H2O. By enriching Tyr of Ac-Asn-Pro-Tyr-NHMe with 15N, it has been possible to distinguish between the resonances of the two side-chain β protons of Tyr. Analysis of the coupling constants in terms of the distributions of side-chain conformations in these peptides indicates that the addition of Asn to the Pro-Tyr sequence leads to a less random conformational distribution. When compared to the side-chain rotamer distribution of Ac-Asn-NHMe and Ac-Tyr-NHMe, particular Asn and Tyr side-chain conformations of Ac-Asn-Pro-Tyr-NHMe are stabilized in dimethylsulfoxide solution. The interaction(s) which stabilize a unique Tyr side-chain conformation of Ac-Asn-Pro-Tyr-NHMe in dimethylsulfoxide are not present in Ac-Ala-Pro-Tyr-NHMe and are unaffected by the addition of Val-Pro to the C-terminus of Asn-Pro-Tyr. In water, a preferential stabilization of one Asn side-chain conformation of Ac-Asn-Pro-Tyr-NHMe is also observed, while the Tyr side-chain rotamer distribution is similar to that of Ac-Tyr-NHMe. An interaction between the Asn side chain and the Pro-Tyr-NHMe backbone was previously shown to stabilize a β-bend conformation at Pro-Tyr in water. Data are also presented for Ac-Tyr-Pro-Asn-NHMe, for which local interactions do not stabilize particular backbone conformations in dimethylsulfoxide or in water. The conformations of the peptides studied here are relatively insensitive to temperatures between 27° and 62°, both in dimethylsulfoxide and in water. The sequences Asn-Pro-Tyr and Tyr-Pro-Asn occur in ribonuclease A, and these tripeptides serve as models for the interactions involved in the folding of this protein. 相似文献
996.
Rainer Büscher Wilhelm Erdbrügger Thomas Philipp Otto-Erich Brodde Martin C. Michel 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(6):592-598
We have compared the coupling mechanisms of rat renal 1A- and 1B-like adrenoceptors to inositol phosphate formation. The experiments were performed in parallel in native renal tissue preparations and in those where 1B-adrenoceptors had been inactivated by treatment with 10 mol/l chloroethylclonidine for 30 min at 37°C; renal slices were used in most experiments but isolated renal cells were also used in some cases. The Ca2+ chelating agent, EGTA (5 mmol/l), reduced noradrenaline-stimulated inositol phosphate formation in native but enhanced it in chloroethylclonidine-treated renal slices. The inhibitory effect of EGTA was not mimicked by 100 nmol/l nifedipine. Inactivation of 87% of cellular Gi by 16–20 h treatment with 500 ng/ml pertussis toxin did not significantly affect noradrenaline-stimulated inositol phosphate formation in isolated renal cells but abolished the inhibitory effect of chloroethylclonidine. The adenylate cyclase activator, forskolin (20 mol/l), inhibited noradrenaline-stimulated inositol phosphate formation in native and chloroethylclonidine-treated slices, and the inhibitory effects of chloroethylclonidine treatment and forskolin were additive. We conclude that in rat kidney inositol phosphate formation via 1B-like adrenoceptors may involve the influx of extracellular Ca2+ and a pertussis toxin-sensitive G-protein but is insensitive to inhibition by forskolin. In contrast 1A-like adrenoceptor-mediated inositol phosphate formation does not require the presence of extracellular Ca2+ or of Gi and is sensitive to inhibition by forskolin. In comparison to published data from other model systems we further conclude that the signaling mechanisms of 1-adrenoceptor subtypes may depend on their cellular environment. 相似文献
997.
Harald Schwörer Andreas Reimann Giuliano Ramadori Kurt Racké 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(4):375-379
The nature of the histamine receptor mediating inhibition of 5-HT release was investigated in strips of the porcine small intestine by investigating the effects of histamine ligands on the overflow of endogenous 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). The overflow was measured by HPLC, combined with electrochemical detection and represents calcium-sensitive 5-HT release from enterochromaffin cells, as reported previously. The histamine H3 receptor selective agonists (R)--methyl-histamine and imetit inhibited the overflow of 5-HT maximally by 50–60%, with EC50 values of 48 and 3.2 nmol/l, respectively. Effects on 5-HT overflow were always accompanied by similar effects on the overflow of 5-HIAA. Thioperamide (100 nmol/l) shifted the concentration response curve of (R)--methyl-histamine to the right (pKB value 8.38). The inhibitory effect of 1 mol/l (R)--methyl-histamine was antagonized in a concentration-dependent manner by thioperamide (IC50: 65 nmol/l) and dimaprit (IC50: 8.6 mol/l); however, the effect of (R)--methyl-histamine was weakly antagonized by burimamide (by 38% at 100 mol/l) and not significantly affected by other H3 receptor antagonists, such as impromidine, betahistine and phenylbutanoyl-histamine (each up to 100 mol/l). In conclusion, H3 receptors mediating inhibition of 5-HT release from porcine enterochromaffin cells have a particular pharmacological profile indicating that heterogeneity of H3 receptors may exist. The data suggest that histamine H3 receptors modulating 5-HT release in pig small intestine do not belong to either H3A or H3B receptors as defined in rat tissue.
Correspondence to: K. Racke at the above address 相似文献
998.
Tuntland Tove Ravasco Rashid J. Al-Habet Sayed Unadkat Jashvant D. 《Pharmaceutical research》1994,11(2):312-317
To determine if there is active efflux of zidovudine (ZDV) and 2,3-dideoxyinosine (ddl) out of the cerebrospinal fluid (CSF), and if this efflux is saturable, we investigated the steady-state CSF/plasma concentration ratio of the two drugs when administered alone or in combination. Constant-rate infusions of ZDV, ddl or both were administered to seven macaques (Macaca nemestrina) through a chronic venous catheter for a minimum of 28 hr. Antipyrine, a marker of passive diffusion, was coinfused in all experiments. Blood (5 mL) and CSF samples (0.5–1 mL) were collected by venous and lumbar/thoracic punctures, respectively, at 24 and 28 hr after beginning the infusion. When ZDV and ddl were administered alone, the steady-state CSF/plasma concentration ratios were significantly different from unity (ZDV, 0.20 ± 0.08; ddI, 0.09 ± 0.04) and were independent of the plasma concentration (P > 0.05). In contrast, the CSF/plasma concentration ratio of antipyrine (0.82 ± 0.19) was close but significantly smaller than unity (P > 0.05). The CSF/ plasma concentration ratios after simultaneous administration of ZDV and ddI were not significantly different (P > 0.05) from those obtained after administration of the drugs alone. These results suggest that ZDV and ddI are actively transported out of the CSF; however, within the concentration range studied, this efflux is neither saturable nor mutually competitive. Concomitant administration of ZDV and ddI did not produce a systemic interaction in the animals, indicating that the pharmacokinetics of either drug is unaffected by the presence of the other. 相似文献
999.
Pharmaceutical Research - 相似文献
1000.
Istvan Máttyus M. Miltényi L. B. Zimmerhackl A. Schwarz M. Hentschel M. Brandis T. Tulassay 《Pediatric nephrology (Berlin, Germany)》1994,8(3):304-308
Urinary excretion of endothelin was measured by radioimmunoassay in children with diabetes mellitus during severe ketoacidosis and 12 days later when blood pH and blood glucose concentrations were normal. Metabolically stable diabetic children served as controls. Results from apparently healthy children without diabetes mellitus were used as normal values. Renal tubular injury was evaluated by the urinary excretion of the proximal tubular marker 1-microglobulin and the distal tubular marker Tamm-Horsfall protein (THP). During ketoacidosis we detected a decreased glomerular filtration rate associated with highly significant changes in the excretion of 1-microglobulin, indicating proximal tubular damage, and THP, suggesting disturbance of cells of the ascending loop of Henle. The daily excretion of endothelin was unaltered but the ratio of endothelin/creatinine or endothelin excretion/creatinine clearance were significantly enhanced. In conclusion, we could demonstrate that, despite a proximal and distal tubular cell dysfunction, endothelin excretion when related to creatinine clearance may be a consequence of disturbed proximal tubular function or dysfunction of the renal medulla. 相似文献