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1.
A. M. Cashmore M. S. Albury C. Hadfield P. A. Meacock 《Molecular & general genetics : MGG》1988,212(3):426-431
Summary The yeast 2 m circle encodes four major transcribed open reading frames, A, B, C and D. Products of ORF's A, B and C, together with the inverted repeats and the other cis-acting loci ORI and STB, have been shown to be involved in plasmid maintenance. However, the function of ORF D has remained unclear. We have therefore carried out studies on 2 m derivatives with both insertional and frameshift mutations in D. Our results indicate that there is a protein product encoded by ORF D, which is involved in plasmid maintenance. When the copy number of the C gene was reduced to one, by chromosomal integration, we observed striking differences in the efficiency of partitioning of D
+ and D
– plasmid derivatives. Absence of D function could be compensated by an increase in dosage of the C gene, indicating that the D product may act to regulate C expression. Since the C product has been implicated in copy number control as well as partitioning, our data suggest that the D product may also be involved in both of these processes. 相似文献
2.
In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera9. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo10,11, which has been tentatively attributed to its unblocking activity8,9 or, possibly, to a complement-dependent cytotoxicity10. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity9,10. 相似文献
3.
4.
Julie A. Woods John A. Hadfield Alan T. McGown Brian W. Fox 《Bioorganic & medicinal chemistry》1993,1(5)
Bis(2-bromo-4,5-dimethoxyphenyl)sulfide (5) and bis(2-bromo-4,5-dimethoxyphenyl) selenide (7) have been shown to block cells in the G2/M phase of the cell cycle, whereas the debromo (4, 6) equivalents do not. The dibromoselenide (7) is cytotoxic to tumour cells in vitro and has been shown to increase the mitotic index of treated cells. These biological effects are consistent with disruption of the mitotic apparatus. This agent does not inhibit microtubule assembly in vitro, but does bind to tubulin. Molecular modelling of these structures indicates that their spatial and electronic structures may make an important contribution to the biological activity. 相似文献
5.
On the mechanism of ATP-induced shape changes in the human erythrocyte membranes: the role of ATP
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In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell. 相似文献
6.
Edward L. Schwartz Anthony F. Hadfield Alfred E. Brown Alan C. Sartorelli 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1983,762(4):489-497
Two analogs of N-acetylmannosamine, (Ac4-NAcMan) and the 2-trifluoroacetamido derivative (Ac4F3-NAcMan), were synthesized as potential inhibitors of the formation of sialic acid-containing glycoconjugates and were examined for their ability to modify the incorporation of into cellular glycoconjugates of Friend murine erythroleukemia cells. Ac4F3-NAcMan and Ac4-NAcMan inhibited cellular replication in suspension culture at concentrations of 0.02 and 0.08 mM, respectively. The cytotoxicity of Ac4-NAcMan was relatively reversible, whereas that produced by Ac4F3-NAcMan was not, as judged by measurement of the cloning efficiencies of cells exposed to these agents. The analogs inhibited incorporation of into ethanol-soluble and -insoluble materials. Separation of ethanol-soluble metabolites by HPLC demonstrated that Ac4F3-NAcMan caused accumulation of radioactivity from in CMP-N-acetylneuraminic acid (CMP-NeuNAc) equal to the decrease in macromolecular-bound 3H caused by this agent. In contrast, similar exposure to Ac4-NAcMan produced a large increase in the amount of radioactivity in ethanol-soluble N-acetylneuraminic acid while decreasing the amount of label from in cellular CMP-NeuNAc, suggesting that the analogs differ in their biochemical sites of action. Treatment of cells with either analog increased the amount of neuraminidase-hydrolyzable sialic acid-like material on the cell surface; this appeared to be due to the incorporation of the analogs into cellular glycoconjugates, since incubation of cells with 3H-labeled analogs resulted in the appearance of radioactivity in cellular ethanol-insoluble and neuraminidase-hydrolyzable material. Incubation of cells with Ac4-NAcMan labeled with 14C in the 4-O-acetyl group further demonstrated that incorporation occurred with approx. 50% retention of this substituent. Thus, both the amount and the nature of the surface sialic acid constituents of treated cells were altered, suggesting that these or similar analogs could potentially be used to modify cellular membrane function. 相似文献
7.
Methyl 2,6-dideoxy-α-L-arabino-hexopyranoside (6) was prepared from L-rhamnose in five steps. Hydrolysis of6 with 50% aqueous acetic acid gave 2,6-dideoxy-L-arabino-hexopyranose. Treatment of 3,4-di-O-acetyl-L-rhamnal with acetic acid in the presence of acetic anhydride and 2% sulfuric acid afforded 1,2,3-tri-O-acetyl-2,6-dideoxy-L-arabino-hexopyranose in 65% yield. Selective benzoylation and subsequent mesylation of 6 afforded methyl 3-O-benzoyl-2,6-dideoxy-4-O-mesyl-α-L-arabino-hexopyranoside, which was treated with sodium benzoate and sodium azide in hexamethylphosphoric triamide to give the corresponding 3,4-dibenzoyl 9 and 4-azido 11 analogs. Hydrogenation and N-acetylation of 11 afforded the 4-acetamido derivative 12. Deprotection of 9 and 12 gave 2,6-dideoxy-L-lyxo-hexopyranose and 4-acetamido-2,4,6-trideoxy-L-lyxo-hexopyranose, which were characterized as their peracetates. The free and corresponding peracetylated derivatives were assayed for their ability to inhibit the growth of P388 leukemia cells in culture. Although the free sugars did not inhibit the replication of these tumor cells under the conditions employed, their peracetylated derivatives demonstrated significant activity. 相似文献
8.
9.
Selective acid-catalysed methanolysis of 2,3,2′,3′-tetra-O-benzyl-4,6:4′,6′-di-O-benzylidene-α,α-trehalose yielded the monobenzylidene derivative, which was converted into the 4,6-dimesylate. Selective nucleophilic displacement of the primary sulphonyloxy group then gave 2,3-di-O-benzyl-6-deoxy-6-fluoro-4-O-mesyl-α-d-glucopyranosyl 2,3-di-O-benzyl-4,6-O-benzylidene-α-d-glucopyranoside. Removal of the protecting groups then yielded 6-deoxy-6-fluoro-α,α-trehalose. In addition, 6-deoxy-6-fluoro-4-O-mesyl-α,α-trehalose and a derivative of 4-chloro-4,6-dideoxy-6-fluoro-α-d-galactopyranosyl α-d-glucopyranoside were also prepared from the same substrate. Iodide displacement of 2,3-di-O-benzyl-4,6-di-O-mesyl-α-d-glucopyranosyl 2,3-di-O-benzyl-4,6-di-O-mesyl-α-d-glucopyranoside afforded the 6-iodide and 6,6′-di-iodide in yields of 31 and 36%, respectively. Similarly, the 6-azide and 6,6′-diazide were isolated in yields of 17 and 21%, respectively. 相似文献
10.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献