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:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two chicken monoclonal antibodies (MAbs), HU/Ch2-7 and HU/Ch6-1, against heterophil Hanganutziu-Deicher (HD) antigens with N-glycolylneuraminic acid (NeuGc) at a terminal carbohydrate were established by cell fusions using chicken B cell lines lacking thymidine kinase and spleen cells from chickens immunized with II3NeuGc alpha-LacCer (HD3). The reactivities of these MAbs against several gangliosides including NeuGc-containing glycosphingolipids were examined by a thin-layer chromatography/immunostaining method. MAb HU/Ch2-7 (IgG) reacted strongly with HD3 and IV3NeuGc alpha-nLc4Cer (HD5) and weakly with VI3NeuGc alpha-nLc6Cer (HD7) and 4-O-acetyl-HD3. HU/Ch6-1 (IgG) reacted with HD3 and HD5, but did not react with the other HD antigens. The reactivities of these MAbs against HD antigen were greatly reduced by pre-treatment of the antigen with neuraminidase. These MAbs did not react with N-acetylneuraminic acid-containing gangliosides (GM1 and GM3). These results indicate that these two chicken MAbs are directed toward the antigenic epitope containing the NeuGc.
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PMID:Two chicken monoclonal antibodies specific for heterophil Hanganutziu-Deicher antigens. 137 80

cDNA clones containing the complete coding sequences for the human parainfluenza virus type 3 (PIV3) fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein genes were inserted into the thymidine kinase gene of vaccinia virus (WR strain) under the control of the P7.5 early-late vaccinia virus promotor. The recombinant vaccinia viruses, designated vaccinia-F and vaccinia-HN, expressed glycoproteins in cell culture that appeared to be authentic with respect to glycosylation, disulfide linkage, electrophoretic mobility, cell surface expression, and, in the case of the HN protein, biological activity. Cotton rats inoculated intradermally with vaccinia-HN developed serum neutralizing antibody titers equal to that induced by respiratory tract infection with PIV3, whereas animals receiving vaccinia-F had threefold lower neutralizing antibody titers. A single immunization with either recombinant vaccinia virus induced nearly complete resistance in the lower respiratory tract of these animals. With regard to protection in the upper respiratory tract, animals immunized with vaccinia-HN or vaccinia-F exhibited reductions in PIV3 replication of greater than 3,000-fold and 6-fold, respectively. This large difference (greater than 500-fold) in reduction of PIV3 replication in the upper respiratory tract was in contrast to the relatively modest difference (3-fold) in serum neutralizing antibody titers induced by vaccinia-HN versus vaccinia-F. This dissociation between the level of neutralizing antibodies and protection suggested that immunity to PIV3 is complex, and that immune mechanisms other than serum neutralizing antibodies make important contributions to resistance to infection. Overall, under these experimental conditions, vaccinia-HN induced a substantially more protective immune response than did vaccinia-F.
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PMID:Expression of the F and HN glycoproteins of human parainfluenza virus type 3 by recombinant vaccinia viruses: contributions of the individual proteins to host immunity. 282 51

The inherited human disorders sialidosis and galactosialidosis are the result of deficiencies of glycoprotein-specific alpha-neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18; sialidase) activity. Two genes were determined to be necessary for expression of neuraminidase by using human-mouse somatic cell hybrids segregating human chromosomes. A panel of mouse RAG-human hybrid cells demonstrated a single-gene requirement for human neuraminidase and allowed assignment of this gene to the (pter----q23) region of chromosome 10. A second panel of mouse thymidine kinase (TK)-deficient LM/TK- -human hybrid cells demonstrated that human neuraminidase activity required both chromosomes 10 and 20 to be present. Analysis of human neuraminidase expression in interspecific hybrid cells or polykaryocytes formed from fusion of mouse RAG (hypoxanthine/guanine phosphoribosyltransferase deficient) or LM/TK- cell lines with human sialidosis or galactosialidosis fibroblasts indicated that the RAG cell line complemented the galactosialidosis defect, but the LM/TK- cell line did not. This eliminates the requirement for this gene in RAG-human hybrid cells and explains the different chromosome requirements of these two hybrid panels. Fusion of LM/TK- cell hybrids lacking chromosome 10 or 20 (phenotype 10+,20- and 10-,20+) and neuraminidase-deficient fibroblasts confirmed by complementation analysis that the sialidosis disorder results from a mutation on chromosome 10, presumably encoding the neuraminidase structural gene. Galactosialidosis is caused by a mutation in a second gene required for neuraminidase expression located on chromosome 20.
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PMID:Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders. 308 2

Two hundred and thirty virus-induced polypeptides have been detected in BHK cells infected with herpes simplex virus type 1 (HSV-1; strain 17) by means of two-dimensional gel electrophoresis. The polypeptides have been characterized by both relative mobility following isoelectric focusing and apparent mol. wt. in SDS-polyacrylamide gels. Some polypeptides, visualized as a single band on a one-dimensional SDS-polyacrylamide gel, were resolved into several spots. Three were identified in Vmw43, the band thought to contain thymidine kinase activity. Not all the observed polypeptides are unique species: some appear to be related and have altered mobilities as a consequence of post-translational modification events. Pulse-chase experiments and treatment of infected cells with neuraminidase suggested that glycoproteins gB, gC and gD contain sialic acid and that synthesis of gB and gD occurs by at least 15 and 10 discrete steps respectively.
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PMID:Two-dimensional gel analysis of HSV type 1-induced polypeptides and glycoprotein processing. 626 77

A suppressive B-cell factor (SBF)-producing hybridoma termed TS-4.44 was established by fusion of B cells which possessed receptors for the Fc portion of IgG (FcR gamma + B cells) and thymidine kinase defective fibroblasts, 3T3-4E cells. The biological properties of hybridoma-produced SBF (Hyb-SBF) are almost the same as those of conventionally prepared SBF (Conv-SBF). Hyb-SBF suppresses (i) plaque-forming cell (PFC) responses in an antigen non-specific manner, (ii) DNA synthesis of lipopolysaccharide (LPS)-activated B cells, but neither concanavalin A (Con A) nor phytohaemagglutinin (PHA)-induced activation of T cells, and (iii) the proliferation of B, but not non-B tumour cells. Once absorbed with L-1210 cells, Hyb-SBF failed to inhibit both PFC and LPS responses. It is important is that Hyb-SBF suppresses the proliferation of L-1210 cells not only in vitro, but also in vivo. The physicochemical properties of Hyb-SBF such as sensitivity to trypsin, pronase and neuraminidase and its molecular weight (43,000), as judged by gel filtration and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) are in accord with those of Conv-SBF. Moreover, it is eluted from a DEAE cellulose column with 0.1-0.3 M phosphate buffer. Thus, monoclonal SBF is thought to be identical with Conv-SBF and could provide us with sufficient material for the analysis of FcR-dependent immunoregulation including surveillance mechanisms controlling the proliferation of B tumour cells.
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PMID:Monoclonal SBF produced by a hybridoma: in-vitro and in-vivo suppression of B tumour-cell proliferation. 636 Aug 50

When chickens were vaccinated with a recombinant fowlpox virus (FPV) containing the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) cDNA under the control of the thymidine kinase (TK) promoter and inserted into the FPV TK gene, the FPV antibody response to the recombinant virus was similar to the response to vaccination with standard FPV, and the recombinant virus protected chickens against challenge with virulent FPV. While the presence of the NDV HN cDNA was demonstrated in the recombinant virus, which was stable on serial passage, expression of HN was not detected by hemagglutination, Western blot analysis or immunoprecipitation of infected cell lysate. Chickens vaccinated with the recombinant virus failed to mount an NDV hemagglutination-inhibition antibody response, and they did not resist challenge with velogenic NDV. It was concluded that the TK promoter was too weak to drive the HN gene, but that the insertion into the FPV TK gene did not reduce the immunogenicity of the virus.
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PMID:Vaccination of chickens with a recombinant fowlpox virus containing the hemagglutinin-neuraminidase gene of Newcastle disease virus under the control of the fowlpox virus thymidine kinase promoter. 788 64

A p7.5/beta-galactosidase (7.5 lacZ) gene construct, cloned adjacent to the fowlpox virus (FPV) thymidine kinase (tk) gene was used as a marker to identify the products of recombination as 'blue' FPV plaques. The rFPVs were detected as early as 4 h after the introduction of plasmid DNAs and by 72 h post-infection (p.i.) for one transfer vector comprised 0.48% of the viral population. The proportion of rFPV increased linearly from 0.073% to 0.62% as the cumulative length of homologous sequences in the transfer vector increased from 0.73 to 4.5 kb. Two approaches using a second reporter gene, the Newcastle disease virus haemagglutinin-neuraminidase (NDV HN) gene were tested to differentiate between single and double cross-over events. In one, the HN gene was cloned into the FPV tk gene and the 7.5 lacZ cloned outside of the homologous region. Progeny of a single cross-over with FPV DNA generated an unstable plaque containing the HN gene and subsequent intramolecular recombination resulted in excision of the 7.5 lacZ and the generation of a stable 'white' plaque. For virus grown in CEF cells (tk+) in the presence of 5-bromo-deoxyuridine, only those viruses which contained a tk gene disrupted by the HN gene formed plaques. This approach allowed us to easily identify rFPV containing the HN gene but lacking 7.5 lacZ or other bacterial sequences. In a second approach, a double cross-over between rFPV DNA containing a stably expressed beta-galactosidase gene cloned into the tk gene (blue plaque) and plasmid DNA containing the HN gene flanked by tk sequences would allow transplacement of the 7.5 lacZ gene with the HN gene, and generating a white plaque. We were unable to generate recombinant viruses with the HN gene and which generated a white plaque, indicating that double cross-over events do not occur at a sufficiently high frequency in FPV.
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PMID:Studies of fowlpox virus recombination in the generation of recombinant vaccines. 807 11

Establishment of selective antiviral chemotherapy has achieved dramatic improvement of the prognosis of several viral infections. It has been considered for a long time that, unlike bacterial infections, viral diseases cannot be successfully treated with chemotherapeutic agents, since viral replication mostly depends on the host-cellular machinery. In fact, some compounds were reported to inhibit viral replication even in the 1950s and 1960s, yet they were also quite toxic to the host cells. The first antiviral compound that strongly inhibits viral replication without affecting the uninfected cells is the anti-herpes agent acyclovir (ACV), which was discovered in the 1970s. Furthermore, in the 1980s, the world-wide epidemic of AIDS caused by human immunodeficiency virus type 1 (HIV-1) infection has dramatically accelerated the development of new antiviral agents. At present, most of the effective antivirals are targeted at virus-specific enzymes, such as ACV for herpes virus thymidine kinase, zidovudine for HIV-1 reverse transcriptase, squinavir for HIV-1 protease, and oseltamivir for neuraminidase of influenza virus. These agents can be administered systemically without serious side effects. However, several drawbacks, including delayed toxicity and drug-resistance, are associated with long-term treatment with several antiviral agents mostly in highly active antiretroviral therapy for HIV-1 infection. Thus, it seems still mandatory to continue the search for more effective and less toxic compounds against various viral infections.
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PMID:[Advances in antiviral chemotherapy]. 1630 32

The identification of small molecules with selective bioactivity, whether intended as potential therapeutics or as tools for experimental research, is central to progress in medicine and in the life sciences. To facilitate such study, we have developed a ligand-based program well-suited for effective screening of large compound collections. This package, MED-SuMoLig, combines a SMARTS-driven substructure search aiming at 3D pharmacophore profiling and computation of the local atomic density of the compared molecules. The screening utility was then investigated using 52 diverse active molecules (against CDK2, Factor Xa, HIV-1 protease, neuraminidase, ribonuclease A, and thymidine kinase) merged to a library of about 40,000 putative inactive (druglike) compounds. In all cases, the program recovered more than half of the actives in the top 3% of the screened library. We also compared the performance of MED-SuMoLig with that of ChemMine or of ROCS and found that MED-SuMoLig outperformed both methods for CDK2 and Factor Xa in terms of enrichment rates or performed equally well for the other targets.
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PMID:MED-SuMoLig: a new ligand-based screening tool for efficient scaffold hopping. 1747 21

Virtual ligand screening methods based on the structure of the receptor are extensively used to facilitate the discovery of lead compounds. In the present study, we investigated the LigandFit package on four different proteins (coagulation factor VIIa, estrogen receptor, thymidine kinase, and neuraminidase), a relatively large compound collection of 65,560 unique "drug-like" molecules and four focused libraries (1950 molecules each). We performed virtual screening experiments with the large database and evaluated six scoring functions available in the package (DockScore, LigScore1, LigScore2, PLP1, PLP2, and PMF). The results showed that LigandFit is an efficient program, especially when used with LigScore1. Similar computations were carried out using focused libraries. In this situation the LigScore1 scoring function outperformed the other ones on three out of the four proteins tested. Even for the difficult neuraminidase case, the LigandFit/LigScore1 combination was still reasonably successful. Assessment of docking accuracy was also performed and again, we found that LigandFit (with DockScore and the CFF parameters) was performing well. On the basis of these results and observed increased enrichments after LigandFit/Ligscore1 screening on focused libraries, we suggest that using this program as a final step of a hierarchical protocol can be very beneficial to assist lead finding.
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PMID:Structure-based virtual ligand screening with LigandFit: pose prediction and enrichment of compound collections. 1751 Sep 58


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