Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine leukemia viruses, such as Rauscher leukemia virus (RLV), contain a proteolytic factor which becomes activated after detergent treatment of the virus. This factor specifically cleaves P70, the gag precursor polyprotein which is enriched for in preparations of immature virus core subparticles. The factor has been partially purified on Sephadex G-75 columns. It has a molecular weight of 10,000-12,000 daltons but does not coincide in elution position with the major peaks of the viral polypeptides p10 or p12. Under optimal conditions, that is 2% NP-40 (v/v), 10 mM DTT, (pH 7.2) and incubation for 16 hr at 22 degrees C, cleavage of labeled P70 occurs and increasing amounts of the four gag polypeptides p30, p15, p12 and p10 are obtained. The P70 cleavage activity is blocked by TLCK, TAME, CBZ-lysine and other lysyl-containing protease inhibitors. Further, the CBZ-lysine inhibition is reversible, while an inhibition by phenyl-methylsulfonyl fluoride (PMSF) is irreversible. These inhibition studies suggest that a similarity exists between the P70 proteolytic factor and some serine proteases, such as trypsin. The cleavage pattern of P70-rich immature cores treated with trypsin or chymotrypsin is different from that obtained with the P70 proteolytic factor. Thus murine leukemia virions apparently contain a unique, highly specific protease which is present in small amounts and cleaves P70.
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PMID:Properties of a P70 proteolytic factor of murine leukemia viruses. 7 13

Lymphoid cells obtained from spleens of patients with lymphomas or leukemias were studied for the presence of heterophile (Paul-Bunnell (P-B)) antigen. A mixed agglutination (MA) test was established utilizing monolayers of cells attached to poly-L-lysine-coated wells of plastic U plates. After incubation of the monolayers with infectious mononeucleosis (IM) sera, indicator cells, sheep, or trypsinized bovine erythrocytes were added. The results were assessed according to sedimentation patterns of the indicator cells on the monolayers. Positive MA reactions were shown to be due to specific binding of P-B antibodies to the corresponding antigens on the spleen cells. Positive results were obtained with 15 of 37 spleens from patients with Hodgkin's disease, 5 of 8 lymphoma spleens, 4 of 15 chronic myelocytic leukemia spleens and 2 of 4 chronic lymphocytic leukemia spleens. Only 2 of 25 spleens from patients with various other diseases and 1 of 26 apparently normal thymus specimens gave positive results. This study confirmed demonstration of P-B antigen in lymphoma and leukemia by means of absorption experiments, which was reported previously.
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PMID:Paul-Bunnell antigen in lymphoma and leukemia spleens. 26 81

In vitro studies were made on four synthetic polymeric derivatives of the antitumor agent methotrexate (MTX): 1) divinylether-maleic anhydride-MTX (DIVEMA-MTX), 2) poly-L-lysine-MTX (PL-MTX), 3) polyethyleneimine-MTX (PEI-MTX), and 4) carboxymethyl cellulose-MTX (CMC-MTX). They were tested for their ability to inhibit tetrahydrofolate dehydrogenase (dihydrofolate reductase). Their growth inhibition of murine L5178Y leukemia cells was also studied. 1wo of these polymers, DIVEMA-MTX and PEI-MTX, had similar or only slightly reduced activity compared to equivalent concentrations of MTX, whereas PL-MTX and CMC-MTX had significantly higher (1--3 logs) minimal inhibitory concentrations.
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PMID:In vitro inhibitory effects of polymer-linked methotrexate derivatives on tetrahydrofolate dehydrogenase and murine L5178Y cells. 28 2

We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 x 10(3)) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells. White Swiss mice show nearly a 100% remission from subsequent tumor growth. Rechallenge of "cured" animals with tumor cells, however shows no long-term immunological protection. In tissue culture, poly(L-lysine) shows a related potent cytotoxicity with HeLa cells; interestingly, the D isomer. In addition, there is a strong molecular weight dependence in that the small polylysine (Mr 3 x 10(3)) possesses less than 1/20th the cytotoxicity of large polymers (Mr 70 x 10(3)) on a weight basis in both cell culture and animal studies. At the same time, none of these lysine polymers gives any significant increase in life span to BDF1 mice infected with L1210 murine leukemia cells. We have also further explored the mechanism by which the polylysines express their cytotoxicity. These data indicate that lysine polymers show cell specificity in their action and in some cases they may be beneficial as potent antineoplastic agents, particularly when molecular weight is taken into consideration.
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PMID:Antineoplastic activity of poly(L-lysine) with some ascites tumor cells. 29 Oct

The metabolism of 14C-lysine by leukaemic cells in acute myeloblastic, myelomonocytic, lymphoblastic and chronic myeloid leukaemia with blast crisis was studied. The investigations included lysine metabolism to CO2, lipids, organic acids and nucleotides and its incorporation into cellular proteins. The obtained results were compared with determinations carried out in granulocytes and lymphocytes of healthy subjects. Cells in acute leukaemias metabolized 14C-lysine in a similar range. In relation to normal cells the range of lysine metabolism to lipids in the leukaemic cells was significantly higher (p less than 0.01), while that of organic acids was significantly lower (p less than 0.05). The activity of 14C-lysine metabolism depended on the number of blast cells in the sample and the type of acute leukaemia. Neoplastic cells in blast crisis and in acute myeloblastic leukaemia incorporated more actively 14C-lysine into proteins than cells in acute myelomonocytic and acute lymphoblastic leukaemia (p less than 0.05). Similar differences in lysine metabolism were observed between myelomonocytes and blast cells from acute lymphoblastic leukaemia (p less than 0.05).
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PMID:[Lysine metabolism in acute leukemia]. 29 72

A series of Nepsilon-poly-alpha-glutamyl and Nepsilon-polylysyl derivatives of Nalpha-pteroyllysine and Nalpha-homopteroyllysine, analogues of the naturally occurring gamma-polyglutamyl forms of folate, was prepared and tested as substrates for dihydrofolate reductase and as substrates and inhibitors of thymidylate synthetase. Nalpha-Dihydropteroyl-Nepsilon-(tri-alpha-glutamyl)lysine was 1.8 times as active as Nalpha-dihydropteroyl glutamate (dihydrofolate) as a substrate for L1210 murine leukemia dihydrofolate reductase. N-alpha-Dihydropteroyl-Nepsilon-(di-alpha-lysyl)lysine was 1.2 times as active as dihydrofolate in spite of its strong positive charge. The most active compound tested, Nepsilon-(tert-butyloxycarbonyl)lysine, was 3.5 times as active as dihydrofolate. None of the enzymatically prepared Nalpha-tetrahydropteroyllysine derivatives tested was as active as Nalpha-tetrahydropteroyl glutamate (tetrahydrofolate) as a substrate for E. coli thymidylate synthetase. However, there was a progressive increase in activity with the addition of each alpha-glutamyl residue, the Nepsilon-(penta-alpha-glutamyl)lysine being 88% as active as tetrahydrofolate. Nalpha-Tetrahydropteroyl-Nepsilon-(di-alpha-lysyl)lysine was the most active thymidylate synthetase substrate of the polylysine derivatives, being 67% as active as tetrahydrofolate. Addition or deletion of lysyl residues resulted in diminished activity. It is noteworthy that substrate activity is retained in spite of the positively charged poly(amino acid) side chain. None of the enzymatically prepared tetrahydrohomopteroyl derivatives tested was as active as Nalpha-tetrahydrohomopteroyl glutamate (tetrahydrohomofolate) as an inhibitor of E. coli thymidylate synthetase.
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PMID:Polyglutamyl and polylysyl derivatives of the lysine analogues of folic acid and homofolic acid. 79 72

Techniques are reported for the induction and assay of cytotoxic effector cells capable of specifically lysing hapten-coupled EL4 leukemia targets. It is shown that EL4 cells survive coupling with TNP-sulfonic acid and retain the hapten on their cell surface for a prolonged period of time. Although TNP-EL4 cells are readily lysed by anti-TNP serum in a complement-mediated reaction, they are inefficiently killed in an antibody-dependent cell-mediated reaction. Cytotoxic effector cells, able to lyse TNP-EL4 targets, are induced when C57BL/6 spleen H-2-b cells are cultured with the following cell types which have been coupled with TNP: 1) ALLOGENEIC P815 tumor cells (H-2-d), 2) syngeneic EL4 tumor cells, 3) allogeneic BALB/c spleen cells (H-2-d), 4) syngeneic C57BL/6 spleen cells. Further experiments show that TNP-coupled xenogeneic chicken erythrocytes, which by themselves are unable to induce cytotoxic effectors, are capable of doing so if uncoupled P815 cells are present simultaneously. On the basis of these findings, it can be hypothesized that two stimuli are required for induction of these cytotoxic effector cells--one provided by the hapten, and the other by the P815 cell. Treatment of cytotoxic spleen cells induced by hapten-coupled allogeneic tumor cells with anti-Thy-1 serum and complement abrogates their cytotoxicity, indicating that T cells play a central role in the cytotoxic reaction. TNP-coupled erythrocytes do not serve as targets for these cytotoxic T cells, but do cause competitive inhibition of TNP-EL4 when added to the reaction mixture at high ratios. However, because the inhibition is relatively low, and because no such inhibition can be demonstrated with TNP-lysine, it is concluded that the receptor on the cytotoxic effector cell has a low affinity for hapten. This low affinity could be due to the receptor recognizing an antigen comprising mouse cell surface antigen in addition to the TNP moiety. Supporting this interpretation is the finding that TNP-EL4 cells competitively inhibit cytotoxicity much more efficiently than TNP-CRBC and that even uncoupled EL4 cells inhibit to some extent.
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PMID:Induction and properties of cytotoxic T cells specific for hapten-coupled tumor cells. 80 74

Inosine dialdehyde (IdA), a new antitumor agent presently undergoing clinical evaluation in man, possesses two aldehyde groups that form stable complexes with a variety of biologic molecules containing amino groups. Complex formation of IdA with lysine, glycine, histidine, or bovine serum albumin (BSA) greatly reduces the cytotoxicity of IdA against L1210 leukemia in vitro. Complexes of IdA and BSA exhibit molecular weights ranging from 69,000 to greater than 800,000 as determined by Sephadex G-200 gel filtration, indicating that both aldehyde groups of IdA are functional and can cross-link protein molecules. The cross-linking of plasma proteins and the cross-linking of glycine to BSA were also observed. No interaction of IdA with nucleic acids, nucleic acid bases, or nucleosides was detected. The dialdehyde derivatives of other nucleosides also possessed cross-linking properties.
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PMID:Protein cross-linking properties of the antitumor agent inosine dialdehyde (NSC-118994). 103 30

Arginine-rich and lysine-rich histones were extracted from various cytologic types of leukemic blasts and from preparations rich in normal monocytes. On polyacrylamide disc electrophoresis, the patterns of normal monocyte histones closely resembled those found in acute histiomonocytic leukemia (Schilling type). The electrophoretic patterns of histones obtained from leukemic blasts in acute myelomonocytic leukemia (Naegeli type) were similar to those found in both acute myelobastic leukemia and chronic granulocytic leukemia. The results support the concept that acute myelomonocytic leukemia may be closely related to, or a variant of, acute myeloblastic leukemia, and that acute histiomonocytic leukemia is most probably a monocytic rather than a myeloblastic disorder. In addition to accepted morphologic and enzymatic criteria, the present studies suggest that differences in histone patterns might be useful in further distinguishing between histiomonocytic, myeloblastic, and myelomonocytic leukemias.
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PMID:Histone abnormalities in adult acute leukemias. 105 65

An analysis of red cell membrane proteins in acute and chronic lymphatic leukaemia, Hodgkin's disease, lymphosarcoma, and myeloma was carried out. The electrophoretic pattern after solubilisation in urea or SDS was examined, along with migration on cellulose acetate or acrylamide in different buffers. Protein acid, basic and neutral amino acid percentages were also determined. An increase in low molecular weight and faster anodic migration proteins was noted in the lymphoblastoses, whereas the amino acid spectrum of these proteins showed percent changes in the case of some amino acids, particularly glutamic acid, phosphoserine, lysine and histidine. The alterations observed were compared with those noted previously in other haemoblastoses, congenital haemolytic and anhaemolytic blood diseases, and endoglobular or acquired metabolic defects in a closer assessment of their significance.
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PMID:[Changes in membrane proteins in the erythrocytes of patients with hemolymphoblastosis not directly involving the erythroblastic line]. 106 86


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