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41.
There is a great deal of current interest in the role and importance of chirality in the development of new drugs, but little attention is being paid to the stereochemistry of older drugs. Indeed, many older chiral drugs were introduced without adequate information on their stereochemical identity or composition. We have examined one such drug, the antihypertensive diuretic agent cyclothiazide. Standard sources of drug information and the research literature do not provide data on the stereochemical composition of clinically used cyclothiazide, although scattered reports indicate that the drug may consist of "several stereoisomers." Inspection of the chemical structure of the drug, 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-1,2,4-benzothiadiazin e-7- sulfonamide 1,1-dioxide, shows that it can exist as eight stereoisomers that may form four racemates. Using synthesis, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, chiral and nonchiral high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy, we determined that pharmaceutical cyclothiazide is in fact a mixture of the eight stereoisomers in the form of the four racemates. The two racemates with endo configuration at the norbornene moiety predominate over the exo racemates, and small but significant differences in isomer distribution between different batches of the drug were observed. We urge that in studies of older drugs the stereochemical details be considered. 相似文献
42.
Dr. R. Banerjee Professor Dr. B. C. Bhattacharyya 《Bioprocess and biosystems engineering》1992,7(8):369-374
A newly isolated Rhizopus oryzae was found to exhibit some unusual phenomenon of secreting alkaline protease which was purified and characterized. The molecular weight was determined to be 28,600 dalton in gel electrophoresis. The enzyme is stable in the pH range from 3 to 11 and most active at pH 8. The temperature optimum of this thermostable biocatalyst is at 60 °C. The enzyme is sensitive to metal chelators, most of the metal ions (excepting a few monovalent cations) and inhibitor like PMSF. This indicates that the protease of isolated Rhizopus oryzae falls under alkaline serine group. 相似文献
43.
G Mukherjee D Banerjee D K Bhattacharya G C Chatterjee 《Indian journal of experimental biology》1990,28(6):550-552
Collagen stimulation of blood platelets resulted in significant increases in malondialdehyde (MDA) formation and activity of glucose-6-phosphate dehydrogenase (G6PDH) and a decrease in catalase and glutathione peroxidase (GPx). Retinoic acid (RA) pretreatment did not show any appreciable changes except for a decrease in G6PDH activity as compared with collagen alone. RA pretreatment of human blood platelets resulted in an increase in the activities of catalase and GPx, two important radical scavenging enzymes, with significant decrease in MDA formation when compared with ADP alone. It is suggested that RA has a significant effect on the antioxidant defence system in ADP stimulated platelets but not in the collagen stimulated platelets. 相似文献
44.
Full-length fibrinogen B beta cDNA was subcloned into an expression vector, pBC12BI, and transfected into COS cells. B beta chain expression was measured by pulse-labelling cells with L-[35S]methionine, immunoprecipitating the B beta chain with antibody to fibrinogen and separating the nascent radioactive protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). B beta chain was expressed in transfected COS cells but was not secreted into the medium. Treatment with endoglycosidase H showed that non-secreted B beta chain contains mannose-rich carbohydrates rather than the complex form of carbohydrate which occurs in plasma fibrinogen and indicates that B beta chain is not transported to the Golgi apparatus. In transfected COS cells, antibody to fibrinogen co-immunoprecipitated B beta chain and 78 kDa immunoglobulin-binding protein (BiP) and antibody to BiP immunoprecipitated BiP and nascent B beta chains. Non-secreted B beta chain was degraded intracellularly with a half-life of 5 h by enzymes which were not affected by incubating transfected cells with NH4Cl, which indicates a non-lysosomal pathway of degradation. These studies indicate that B beta chain by itself does not contain the signal for fibrinogen secretion and that non-secreted B beta chain is associated with BiP and degraded in the rough endoplasmic reticulum. 相似文献
45.
The microtubule associated proteins of goat brain were separated from tubulin on the basis of their thermostability and then
fractionated by chromatography on Sepharose 4B column. Analysis of the fractions by SDS-Polyacrylamide gel electrophoresis
and assay of their tubulin-assembly-promoting activity indicate that this activity resides primarily in the tauproteins (mol.
wt. 55,000–70,000) and a class of even lower molecular weight (25,000–35,000) proteins. Electrophoresis of the microtubule
associated protein fractions separated from tubulin by phosphocellulose chromatography are in agreement with the results obtained
from fractionation on Sepharose 4B columns. 相似文献
46.
The molecular conformation of d1-8-isotestosterone has been determined crystallographically. Crystals of the title compound belong to the space group P21/c with a = 11.449(4), b = 10.962(4), c = 25.860(5) , β = 100.95(4)0, with two molecules in the asymmetric unit. The structure has been refined to a final R value of 0.052 for 2227 reflections. Unlike testosterone, which is a flat molecule, its 8-isomer has a folded conformation. The conformations of the ring-B in the two crystallographically independent molecules (A and B) correspond to the twist form and differ significantly from one another. 相似文献
47.
48.
Binding of [3H]dihydroergokryptine and [3H]dihydroalprenolol to membrane preparations from rat submaxillary gland was measured to characterize the alpha- and beta-adrenergic receptors, respectively. Kinetic analysis of the data revealed a high affinity binding site for each radioligand. Inhibition of binding at each site was stereospecific for the active isomer of the catecholamine used. The greater ability of a beta1 than beta2 specific beta-adrenergic antagonist to displace [3H]dihydroalprenolol binding indicated that this binding site was of the beta1 type. Chemical sympathectomy with reserpine or 6-hydroxydopamine resulted in a significant increase in both [3H]dihydroalprenolol and [3H]dihydroergokryptine binding in the rat submaxillary gland. 3scatchard analysis of the data indicated that these increases in binding were due to a change in total number of binding sites for [3H]dihydroergokryptine and [3H]dihydroalprenolol with little change in apparent affinities. This suggests that changes in alpha- and beta-adrenergic receptor density may be important in the development of supersensitivity in salivary glands after reserpine and 6-hydroxydopamine treatment. 相似文献
49.
R K Banerjee 《European journal of biochemistry》1979,97(1):59-64
An adenosine triphosphatase (ATPase EC 3.6.1.3) was partially purified from myeloblasts of chicken infected with the avian myeloblastosis virus and some of its molecular, catalytic and immunological properties were compared with that of the ATPase purified from the virus. Both the enzymes possessed almost same electrophoretic mobility, molecular weight, S20,w value, substrate specificity, metal-ion requirement, apparent Km value and sensitivity to inhibitors and activator. Evidence also indicated immunological identity of the two enzymes. The insensitivity of this enzyme to rutamycin or ouabain and extreme sensitivity to most of the detergents, trypsin and mercurials are the remarkable properties of this enzyme. 相似文献
50.