Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two groups of children with refractory acute lymphoblastic leukemia were treated with a regimen of methotrexate (MTX) and asparaginase (Asn'ase) based on studies of the effect of MTX in vitro on human lymphoblasts exposed to Asn'ase. Induction therapy in 12 children produced 4 complete remissions, 3 partial remissions, and 5 failures. Responsiveness to Asn'ase seemed necessary for successful induction with the drug combinations. Maintenance therapy in 18 children produced a median hematologic remission of 31 weeks (range 3-85 weeks). During remission, 2 children developed central nervous system leukemia and 2 died of infection. The mean maximally tolerated dose of MTX was 361 mg/m2. The results of this trial suggest therapeutic synergy in maintenance therapy and the capability of Asn'ase to attenuate MTX toxicity.
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PMID:Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leukemia of childhood. 28 40

The NH2-terminal amino acid sequence of Moloney murine leukemia virus reverse transcriptase was determined to be Thr-Leu-Asn-Ile-Glu-Asp-Glu-Tyr-Arg-Leu-His-Glu-. The comparison of the amino acid analysis data obtained after carboxypeptidase Y digestion with the published nucleotide sequence (T. M. Shinnick, R. A. Lerner, and J. G. Sutcliffe, Nature (London) 293, 543-548, 1981) led to the conclusion that the COOH-terminus is Leu coded by CTC in nucleotide positions 4608-4610, and the tentative COOH-terminal sequence is Pro-Asp-Thr-Ser-Thr-Leu-Leu-OH. In light of these and previously reported results the complexity and map order of the pol gene are discussed.
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PMID:Amino- and carboxyl-terminal sequence of Moloney murine leukemia virus reverse transcriptase. 241 14

Two human cell lysosomal membrane glycoproteins of approximately 120 kDa, hLAMP-1 and hLAMP-2, were identified by use of monoclonal antibodies prepared against U937 myelomonocytic leukemia cells or blood mononuclear cells. The two glycoproteins were purified by antibody affinity chromatography and each was found to be a major constituent of human spleen cells, representing approximately 0.05% of the total detergent-extractable protein. Both molecules were highly glycosylated, being synthesized as polypeptides of 40 to 45 kDa and cotranslationally modified by the addition of Asn-linked oligosaccharides. NH2-terminal sequence analysis indicated that each was approximately 50% identical to the corresponding mLAMP-1 or mLAMP-2 of mouse cells. Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures but not in the peroxidase-positive granules of monocytes. Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. This cell-surface expression may be differentiation related, since the proteins were not detected in the plasma membrane of normal blood monocytes and their expression on U937 and HL-60 cells was reduced when the cells were treated with differentiating agents. Cell-surface expression of both glycoproteins was markedly increased in blood monocytes but not in U937 cells after exposure to the lysosomotropic reagent methylamine HCl, indicating differences in LAMP-associated membrane flow in these cell types.
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PMID:Purification and characterization of human lysosomal membrane glycoproteins. 291 82

We have used oligonucleotide probes, based on a portion of the p60v-src autophosphorylation sequence, Glu-Asp-Asn-Glu-Tyr-Thr, to identify and characterize a cDNA from the human T-leukemia cell line, JURKAT. The JURKAT cDNA (designated ptk-JURKAT) was homologous to but distinct from the src, yes and fgr oncogenes, which encode protein-tyrosine kinases (ATP:protein phosphotransferase, EC 2.7.1.37). The ptk-JURKAT cDNA hybridized with a 2.2 kb RNA transcript from JURKAT cells and the human T-cell lymphoma line, MOLT-4, but failed to identify any transcript in two human B-cell lymphoma lines or a human erythroid-myeloid leukemia line, K562. Recently the nucleotide sequence has been established for the murine lymphocyte protein tyrosine kinase, p56LSTRA. The ptk-JURKAT cDNA appears to encode the human homolog of p56LSTRA.
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PMID:Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA. 348 86

N-terminal amino acid sequence analysis of the transmembrane protein of baboon endogenous virus revealed an internal 13 residue identity with the transmembrane homolog of murine leukemia virus. A tridecapeptide Glu-Val-Val-Leu-Gln-Asn-Arg-Arg-Gly-Leu-Asp-Leu-Leu corresponding to this region was chemically synthesized and antibody to the peptide was raised in rabbits. The rabbit antisera recognized the protein in Western blots. The specificity of the antisera was tested against a panel of retroviruses. Transmembrane proteins of type C retroviruses as well as type D were identified.
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PMID:Antibody to a synthetic peptide detects a conserved region of retrovirus transmembrane proteins. 397 84

Addition of asparagine-linked oligosaccharides to nascent murine leukemia virus (MuLV)-encoded membrane glycoproteins was inhibited either completely by tunicamycin or specifically at Asn-X-Thr glycosylation sites by incorporation of the threonine analogue beta-hydroxynorvaline. In conditions of partial analogue substitution, a series of subglycosylated components is formed which are related by a constant apparent Mr difference when assayed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The total number of asparagine-linked oligosaccharides is then estimated by dividing the measured apparent Mr of one oligosaccharide into the total apparent Mr difference between the complete glycoprotein and the polypeptide chain that is synthesized in cells incubated with tunicamycin. Correct results were obtained using glycoproteins with known numbers of oligosaccharides. Our analyses indicate that the gp70 membrane envelope glycoproteins of certain ecotropic MuLVs contain seven oligosaccharides, whereas the GIX+ antigen-containing variant gp70 contains one fewer Asn-X-Thr-linked oligosaccharide. The membrane glycoprotein encoded by the gag gene of Friend MuLV contains only one asparagine-linked oligosaccharide. Similarly, the gp55 membrane glycoprotein encoded by Friend erythroleukemia virus contains four asparagine-linked oligosaccharides. Pulse-chase and cell surface iodination analyses indicate that MuLV membrane envelope glycoprotein processing by partial proteolysis and transport to the cell surface can be efficiently blocked by structural perturbations caused by incorporation of different amino acid analogues or by loss of oligosaccharides. Our data also suggest that loss of oligosaccharides may expose new antigenic sites in viral membrane glycoproteins and increase their susceptibility to intracellular proteolysis.
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PMID:Glycosylation and intracellular transport of membrane glycoproteins encoded by murine leukemia viruses. Inhibition by amino acid analogues and by tunicamycin. 629 17

The nucleotide sequence of the envelope gene and the adjacent 3' long terminal repeat (LTR) of Gardner-Arnstein feline leukemia virus of subgroup B (GA-FeLV-B) has been determined. Comparison of the derived amino acid sequence of the gp70-p15E polyprotein to those of several previously reported murine retroviruses revealed striking homologies between GA-FeLV-B gp70 and the gp70 of a Moloney virus-derived mink cell focus-forming virus. These homologies were located within the substituted (presumably xenotropic) portion of the mink cell focus-forming virus envelope gene and comprised amino acid sequences not present in three ecotropic virus gp70s. In addition, areas of insertions and deletions, in general, were the same between GA-FeLV-B and Moloney mink cell focus-forming virus, although the sizes of the insertions and deletions differed. Homologies between GA-FeLV-B and mink cell focus-forming virus gp70s is functionally significant in that they both possess expanded host ranges, a property dictated by gp70. The amino acid sequence of FeLV-B contains 12 Asn-X-Ser/Thr sequences, indicating 12 possible sites of N-linked glycosylation as compared with 7 or 8 for its murine counterparts. Comparison of the 3' LTR of GA-FeLV-B to AKR and Moloney virus LTRs revealed extensive conservation in several regions including the "CCAAT" and Goldberg-Hogness (TATA) boxes thought to be involved in promotion of transcription and in the repeat region of the LTR. The inverted repeats that flanked the LTR of GA-FeLV-B were identical to the murine inverted repeats, but were one base longer than the latter. The region of U3 corresponding to the approximately 75-nucleotide "enhancer sequence" is present in GA-FeLV-B, but contains deletions relative to AKR and Moloney virus and is not repeated. An interesting pallindrome in the repeat region immediately 3' to the U3 region was noted in all the LTRs, but was particularly pronounced in GA-FeLV-B. Possible roles for this structure are discussed.
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PMID:Nucleotide sequence of the envelope gene of Gardner-Arnstein feline leukemia virus B reveals unique sequence homologies with a murine mink cell focus-forming virus. 630 47

The glycoprotein from Friend murine leukemia virus was digested with protease from Staphylococcus aureus V8. A glycopeptide comprising the N-terminal glycosylation site (Asn-12) was isolated from the mixture of fragments and analyzed by amino acid sequencing and methylation-capillary gas chromatography-mass spectrometry before and after treatment with sialidase from Vibrio cholerae. Asn-12 was thus found to be substituted by a family of partially sialylated, fucosylated, and intersected glycoprotein N-glycans of the hybrid type.
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PMID:The glycoprotein 71 of ecotropic Friend murine leukemia virus. Structure of the oligosaccharides linked to asparagine-12. 637 Jul 24

DL-threo-beta-Fluoroasparagine (DL-threo-beta-F-Asn) inhibited the growth of murine leukemia L1210 cells and three human leukemia cell lines in culture. Fifty % inhibiting dose values ranged between 30 and 50 microM DL-threo-beta-F-Asn. L1210 cells were not sensitive to DL-erythro-beta-fluoroasparagine, DL-threo-beta-fluoroaspartic acid, or DL-erythro-beta-fluoroaspartic acid at 300 microM, the highest dose studied. The antileukemia activity of DL-threo-beta-F-Asn was studied in further detail using the L1210 model system. Inhibition of growth in culture was prevented by L-asparagine but not by D-asparagine. Inhibition of growth of L1210 cells incubated for 40 hr in the presence of 300 microM DL-threo-beta-F-Asn was reversed after DL-threo-beta-F-Asn removal. Treatment for longer periods of time resulted in cell lysis. DL-threo-beta-F-Asn at doses of 250 mg/kg increased life span in mice bearing L1210 tumors by 60%. These results demonstrate the chemotherapeutic potential of the amino acid analogue DL-threo-beta-F-Asn.
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PMID:Antitumor activity of DL-threo-beta-fluoroasparagine against human leukemia cells in culture and L1210 cells in DBA mice. 649 22

A modification of the hydroxylamine cleavage of proteins is presented in which proteins were cleaved while immobilized in the matrix of a polyacrylamide gel. The reaction under these conditions retains its high specificity for Asn-Gly bonds and has the advantage that the gel matrix, acting as a carrier, facilitates simultaneous treatment of many samples, and contributes to a high recovery efficiency (60-90%) of the cleavage products. The cleavage is performed with individual protein bands excised from dried slab gels after detection by staining, autoradiography, or fluorography. The procedure can be easily combined with other techniques to further characterize the cleavage fragments. Also a two-dimensional version of the cleavage method was developed, which allows rapid recognition of interrelationships between proteins in a complicated mixture. The versatility of the procedure is demonstrated in a number of applications. Highly related strains of murine leukemia viruses were easily distinguished from one another by the unique cleavage patterns of their gag- and env-precursor polypeptides. Comparing the env-precursor gPr82env synthesized in the presence or absence of tunicamycin with its cell-free synthesized counterpart, revealed the presence of an amino-terminal signal sequence. Cleavage patterns of pro-opiomelanocortin (POMC) from three different species revealed a high degree of homology between rat and mouse POMC, whereas Xenopus POMC was very different. Regions to which carbohydrates are attached could be identified by comparing glycosylated and unglycosylated forms of POMC. Combining the hydroxylamine cleavage procedure with immunological characterization of the fragments showed a small but significant difference between the amino-terminal sequences of the recombinant transforming protein P120 of Abelson murine leukemia virus and of its parent molecule Pr65gag of Moloney murine leukemia virus.
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PMID:Hydroxylamine cleavage of proteins in polyacrylamide gels. 662 62


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