Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.53 (sialidase)
2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid (4-guanidino-Neu5Ac2en), designed with computer assistance and knowledge of the crystal structure of influenza virus neuraminidase, has shown antiviral effects in animal models of human influenza (M. von Itzstein et al., Nature, 363, 418-423, 1993). Here we demonstrate that the compound efficiently inhibits the enzyme activity of all nine subtypes of avian influenza A neuraminidase in vitro. When administered intranasally to chickens infected with lethal viruses, high doses of the compound (1000 micrograms/kg) protected 85% of birds harboring A/Chick/Victoria/1/85 (H7N7), a fowl plague virus, but not chickens infected with other highly virulent viruses of the N1, N2, or N3 subtype. This differential inhibitory effect was also seen in a plaque reduction assay with Madin-Darby canine kidney cells (MDCK), where 4-guanidino-Neu5Ac2en was more effective against A/Chick/Vic/85 (H7N7) than A/FPV/Rostock/34 (H7N1). In contrast to the substantial plaque reduction observed in MDCK cells, the drug failed to inhibit plaque formation in chicken embryo fibroblasts infected with either A/Chick/Vic/85 or A/FPV/Rostock/34, regardless of its concentration. The different levels of drug efficacy seen in two cell systems most likely reflect the location of virus budding and release in polarized versus nonpolarized cells, as well as the compound's mode of extracellular action.
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PMID:Inhibition of replication of avian influenza viruses by the neuraminidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid. 757 1

Erythrocytes adhere to each other when suspended in supra-threshold concentrations of dextran of molecular mass of 40 kD or greater. The plasma membranes are parallel to each other over the entire length of the contact seam at the lower effective polymer concentrations. When cells are pretreated with the proteolytic enzyme pronase or the sialidase neuraminidase the membranes are not parallel but make contact at spatially periodic locations along the membrane surface. Pronase induced reduction of cell electrophoretic mobility rapidly reaches a limiting value. Nevertheless, prolonged pre-exposure to enzyme leads to a continuing reduction in contact separations. This result taken with the observation that, for equal loss of electrophoretic mobility, a shorter contact separation results from pronase rather than neuraminidase pre-treatment implies that a non-electrostatic consequence of pronase pre-treatment dominates membrane interaction in the experimental regimes examined here. The average lateral contact separation for different enzyme regimes lay in the range 3.3 microns to a limiting lower value of about 0.7 micron. There was a good correlation between the logarithm of a contact separation index (the approach of separation distance to its limiting value) against the logarithm of a derived index related to net attractive interaction for a wide range of experimental conditions. Treatments which increased attraction or decreased repulsion (e.g. increased dextrans concentration or enzyme pre-treatment) lead to shorter lateral contact separation. This result is qualitatively consistent with the predicted behaviour for the dominant wavelength arising from interfacial instability of a thin aqueous film between adjacent membranes.
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PMID:Influence of polymer concentration and molecular weight and of enzymic glycocalyx modification on erythrocyte interaction in dextran solutions. 768 91

The partial sequence of a gene encoding the COOH terminus of a protein of apparent molecular weight of 160 kD associated with the flagellum of trypomastigotes of Trypanosoma cruzi (FL-160 now renamed to FL-160-1) has been previously reported. The COOH terminus of FL-160-1 has an epitope, defined by 12 amino acids, which molecularly miMics a nervous tissue antigen of 48 kD found in myenteric plexus, sciatic nerve, and a subset of cells in the central nervous system. We now report that FL-160 is a family of highly related genes. The sequence has been determined for the entire open reading frame (ORF) of one of the members of the FL-160 gene family (FL-160-2) and three other partial ORFs. Sequence analysis reveals the various members of the FL-160 gene family to be approximately 80% homologous in the predicted amino acid sequence, but all retain the 12-amino acid molecular mimicry epitope on the COOH terminus. Comparison of the sequence of FL-160-2 to other sequences demonstrates amino acid homology to bacterial sialidase (27%), members of the SA85 gene family (25-30%) and the shed acute-phase antigen/neuraminidase/trans-sialidase gene family (25-30%). Quantitative hybridization at high stringency suggests 750 copies of FL-160 are present in the DNA of each parasite. Reverse transcription and sequence analysis demonstrates that at least five of the members of the FL-160 gene family are transcribed. The NH2 terminus of one of the FL-160 gene products was expressed and antibodies prepared. Antibodies directed to either the COOH or the NH2 terminus of FL-160 bind a 160-kD T. cruzi protein. Both antibodies bind the surface membrane in the flagellar pocket of the trypomastigote. Antibodies to the NH2 terminus bind epineurium and scattered linear densities in sciatic nerve in a pattern distinct from the pattern with antibodies to the COOH terminus. Thus, there are at least two distinct molecular mimicry epitopes on the FL-160 molecule and both mimic epitopes found in nervous tissues. FL-160 may be involved in the generation of autoimmunity to nervous tissues by molecular mimicry, observed in chronic Chagas' disease.
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PMID:FL-160 proteins of Trypanosoma cruzi are expressed from a multigene family and contain two distinct epitopes that mimic nervous tissues. 768 32

The enzyme N-acylneuraminate glycohydrolase, E.C. 3.2.1.18 (sialidase or neuraminidase) was detected in all five strains of Oerskovia (Cellulomonas) turbata and in a further strain isolated from clinical material. The detection of sialidase was performed by different methods, i.e. colorimetric determination of liberated chromogen, immunoelectrophoresis and paper chromatography. The Oerskovia turbata sialidase is able to cleave different linkages between N-acylneuraminic acid and the carbohydrate chains of oligosaccharides or polysaccharides and of glycoproteins, i.e. the 2-->3, 2-->6, and 2-->8 linkages. Finally, the ecologic and pathogenic role of neuraminidase is discussed.
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PMID:Detection of sialidase activity in Oerskovia (Cellulomonas) turbata. 773 24

We demonstrate the potent antiviral activity of a novel viral neuraminidase (sialidase) inhibitor, 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid (GG167), administered by the intranasal route in comparison with those of amantadine and ribavirin in experimental respiratory tract infections induced with influenza A and B viruses. In an extended study in which mice were infected (day 0) with influenza A/Singapore/1/57 virus, with treatments given prophylactically plus twice daily over days 0 to 3 and with mice observed to day 10, we show that intranasally administered GG167 at 0.4 and 0.01 mg/kg of body weight per dose reduced mortality, lung consolidation, and virus titers in the lung, with no virus growing back following the cessation of treatment. In other studies with influenza B/Victoria/102/85 virus in which infected mice were culled after the cessation of treatment, the calculated intranasal dose required to reduce virus titers in the lungs of treated animals to 10% of that seen in untreated controls (EDAUC10 [where AUC is area under the virus titer days curve]) was 0.085 mg/kg per dose. GG167 was inactive against influenza viruses A and B when given by the intraperitoneal or oral route (EDAUC10, > 100 mg/kg per dose). GG167 was metabolically stable, with an elimination half-life of 10 min following intravenous administration. While readily bioavailable by systemic routes, it was poorly bioavailable by the oral route. Its potent efficacy by the intranasal route but lack of efficacy by other routes, relative to those of amantadine and ribavirin, was explicable in terms of its in vitro activity, bioavailability, and pharmacokinetic properties and with the extracellular activity of viral sialidase.
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PMID:Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). 784 May 56

In light of the ability of B cells treated with neuraminidase to interact more effectively with T cells, the increased capacity of activated, but not small resting B cells, to interact with T cells could be associated with the level of sialylation on certain B cell surface molecules which influences the effectiveness of the physical interaction between B and T cells. The purpose of this study was to determine if activation of B cells altered sialylation via an endogenous sialidase which affected both the initial interaction between T and B cells and subsequent B cell-induced T cell proliferation. The competitive neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), inhibited LPS-mediated enhancement of B cell conjugate formation with Ia-specific T cell clones as well as enhancement of their capacity to stimulate a mixed lymphocyte reaction. The addition of NeuAc2en during LPS stimulation did not affect the surface expression of Ia, LFA-1, ICAM-1 or mB7, suggesting that inhibition of LPS-mediated enhancement by the sialidase inhibitor was not due to changes in the level of expression of the major B cell adhesion or co-stimulatory molecules. Short term stimulation with phorbol myristate acetate (PMA) and ionomycin also enhanced the ability of resting B cells to form antigen specific T:B conjugates. However, activation of B cells with PMA and ionomycin or with LPS did not change the capacity of a sialic acid specific lectin to bind to the B cells, suggesting that activation was not associated with global changes in surface sialic acid content. B cell stimulation did not appear to increase the activity of the most prevalent B cell sialidase activity as measured in an in vitro assay system, suggesting that the major B cell sialidase may not be responsible for the alteration of B cell sialylation levels or the ability of activated B cells to interact more effectively with T cells. The possibility of intracellular compartmentalization of sialidase activity or that a minor B cell sialidase may play a role in the regulation of a B cells ability to interact with T cells are discussed.
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PMID:Regulation of B cell:T cell interactions: potential involvement of an endogenous B cell sialidase. 785 58

Many researches have demonstrated that cultured tissue or cells may reduce immunogenicity and can survive in a recipient if they are allografted or xenografted. The cause for this phenomenon remains uncertain. In this experiment, sialic acid (SA) content of BALB/C mice pituitary cells before and after culture was determined, and the influence of SA level on cell immunogenicity was studied by using the mixed lymphocyte reaction method and neuraminidase. The SA level was much higher in cultured cells than in uncultured cells. Cultured cells were found to have a reduced ability to stimulate splenocyte proliferation in allogeneic rats after the SA levels of the cells had been raised. Such ability could be restored by removing SA from the cell surface with sialidase. This suggests that the high SA levels in the cultured cells play an important role in reducing their immunogenicity.
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PMID:[Influence of sialic acid level in cultured pituitary cells on immunogenicity]. 795 25

The sialidase inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N- acetylneuraminic acid was tested for growth inhibitory effects against a panel of avian influenza A viruses encompassing all nine neuraminidase subtypes. Growth in tissue culture of viruses from each subtype was inhibited by this compound at concentrations within a range previously found effective against human N1 and N2 viruses. This compound may prove a selective agent for the treatment (and prevention) of influenza virus infections.
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PMID:Inhibition of the growth of influenza viruses in vitro by 4-guanidino-2,4-dideoxy-N-acetylneuraminic acid. 799 78

A method for sialidase (neuraminidase; EC 3.2.1.18) measurements in the blood serum and saliva has been developed. The activity of this enzyme in the blood serum manifests in repeated intensive stressogenic exposures, malignant tumors and acute respiratory diseases. Salivary sialidase activity is elevated in the patients with multiple dental caries.
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PMID:[The determination of sialidase activity in the blood serum and saliva]. 803 72

Human leucocytes contain a freeze-stable sialidase (neuraminidase; EC 3.2.1.18) activity in addition to the better-characterized lysosomal freeze-labile enzyme. In order to discriminate between the sialidase activities detected with the synthetic fluorimetric substrate 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (MU-Neu5Ac), different tritiated sialoglycoconjugate substrates were prepared. Using this sensitive radioactive assay system, leucocyte sialidase activity towards glycoproteins was shown to be labile to repeated freeze-thawing, but a Triton-stimulated activity towards gangliosides was entirely freeze-stable. Assay conditions were optimized for this freeze-stable ganglioside sialidase activity. Subcellular fractionation of mononuclear leucocytes (MNLs) on Percoll-density gradients showed that this ganglioside sialidase activity was entirely associated with the plasma membrane. Study of the detergent requirements showed that MNLs also demonstrated ganglioside sialidase activity when sodium cholate was present in place of Triton. Cholate-stimulated ganglioside sialidase activity was found to be entirely freeze-stable and localized at the plasma membrane. Studies on whole homogenates of MNLs demonstrated that the Triton-stimulated and cholate-stimulated activities showed similar acidic pH optima at < or = 3.9 and were both strongly inhibited by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid and Cu2+, but not by free N-acetylneuraminic acid, N-(4-nitrophenyl)oxamic acid or heparan sulphate. These results suggest that human MNLs contain, in addition to the lysosomal freeze-labile sialidase, a single sialidase activity which is freeze-stable, ganglioside-specific, plasma membrane-associated and stimulated both by Triton and by cholate.
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PMID:Freeze-stable sialidase activity in human leucocytes: substrate specificity, inhibitor susceptibility, detergent requirements and subcellular localization. 805 2


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