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1.
Auromomycin and macromomycin from the organism Streptomyces macromomyceticus have been crystallized. The X-ray diffraction pattern of crystals of each molecule is consistent with space group P21212 with cell parameters for auromomycin, and for macromomycin. Diffraction analysis of auromomycin is in progress. 相似文献
2.
Biological activity of the antitumor protein neocarzinostatin coupled to a monoclonal antibody by N-succinimidyl 3-(2-pyridyldithio)-propionate 总被引:6,自引:0,他引:6
Gundram Jung Wolfgang Köhnlein Gerd Lüders 《Biochemical and biophysical research communications》1981,101(2):599-606
The chromophore free apoprotein of neocarzinostatin was coupled to monoclonal IgG1 antibody using N-Succinimidyl 3-(2-pyridyldithio)-propionate as heterobifunctional reagent. After coupling active chromophore was reassociated with the apoprotein. We present here experimental evidence that the hybrid protein retains biological activity as measured by the degradation of T2-DNA and bacteriostatic action. 相似文献
3.
Neocarzinostatin abstracts a hydrogen during formation of nucleotide 5'-aldehyde on DNA 总被引:1,自引:0,他引:1
The oxidative reaction of polydeoxyadenylic-deoxythymidylic acid [poly(dA-dT)] with neocarzinostatin that produces 5'-thymidine aldehyde esterified to the 5'-end of strand breaks proceeds with hydrogen abstraction. The abstracted hydrogen is covalently bound to the non-protein component of neocarzinostatin; only a small amount (5%) is washed out into solvent. These data rule out a peroxyl radical as the primary DNA damaging species involved in the production of the 5'-aldehyde group. In contrast to earlier reports, it is demonstrated that alpha-tocopherol is not an inhibitor of the reaction. 相似文献
4.
Arjan Pol Chris van der Drift Godfried D. Vogels Theo J.H.M. Cuppen Wim H. Laarhoven 《Biochemical and biophysical research communications》1980,92(1):255-260
Syntheses of 7-hydroxy-10-methyl-5-deazaisoalloxazine (7-HMDI) and 8-hydroxy-10-methyl-5-deazaisoalloxazine (8-HMDI) are described. The physicochemical and biological properties of 8-HMDI, in contrast to those of 7-HMDI, are very analogous to those of F420, a coenzyme found in methanogenic bacteria. 相似文献
5.
On the mechanism of reductive activation in the mode of action of some anticancer drugs 总被引:6,自引:0,他引:6
V Favaudon 《Biochimie》1982,64(7):457-475
Bioactivation of a number of DNA-specific antitumor drugs depends on oxidoreduction. Bleomycin, neocarzinostatin and anthracycline glycosides are the best known among such drugs in terms of reductive activation processes. Their reduction results in short-lived radical or electrophilic intermediates attacking DNA stereospecifically. The physico-chemical properties of these drugs and the nature of DNA damage are reviewed. Models for DNA-intercalation, electron-donor systems involved in drug metabolisation, and the role of oxygen in radical reactions, are discussed in the light of recent reports. 相似文献
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7.
An increasing number of proteins are currently available on the market as therapeutics and this branch of the pharmaceutical industry will expand substantially during the coming years. As many diseases result from dysfunction of proteins forming multicomponent complexes, protein drugs with their inherent high specificity and affinity seem to be optimal medical agents. On the other hand, proteins are often highly instable and sensitive to degradation, which questions their applicability as effective therapeutics. Therefore, redesign and engineering of proteins is usually a required step in the present day drug development.Several approaches have been applied to optimize the protein properties central to their pharmaceutical use. This review focuses on different strategies that improve two crucial factors influencing protein drug efficiency: protein stability and its in vivo half-life. We provide examples of successful genetic and chemical modifications applied in the design of effective protein therapeutics. 相似文献
8.
degradation of DNA to acid soluble products was induced by the combined action of neocarzinostatin and sulfhydryl agent as 2-mercaptoethanol, dithiothreitol, or reduced glutathione, but not other reducting agent as ascorbic acid or NaBH4. From the analysis by Sephadex G-10 gel filtration, acid soluble products were found to be thymine and oligonucleotide, but not thymidylic acid and thymidine. Release of adenine or guanine from DNA was not detected.From these results, it is suggested that DNA chain breakage by the combined action of neocarzinostatin and 2-mercaptoethanol may be due to an indirect phosphodiester bond breakage with release of thymine. 相似文献
9.
Gliomas are resistant to radiation therapy, as well as to TNFα induced killing. Radiation-induced TNFα triggers Nuclear factor κB (NFκB)-mediated radioresistance. As inhibition of NFκB activation sensitizes glioma cells to TNFα-induced apoptosis, we investigated whether TNFα modulates the responsiveness of glioma cells to ionizing radiation-mimetic Neocarzinostatin (NCS). TNFα enhanced the ability of NCS to induce glioma cell apoptosis. NCS-mediated death involved caspase-9 activation, reduction of mitochondrial copy number and lactate production. Death was concurrent with NFκB, Akt and Erk activation. Abrogation of Akt and NFκB activation further potentiated the death inducing ability of NCS in TNFα cotreated cells. NCS-induced p53 expression was accompanied by increase in TP53-induced glycolysis and apoptosis regulator (TIGAR) levels and ATM phosphorylation. siRNA-mediated knockdown of TIGAR abrogated NCS-induced apoptosis. While DN-IκB abrogated NCS-induced TIGAR both in the presence and absence of TNFα, TIGAR had no effect on NFκB activation. Transfection with TIGAR mutant (i) decreased apoptosis and γH2AX foci formation (ii) decreased p53 (iii) elevated ROS and (iv) increased Akt/Erk activation in cells cotreated with NCS and TNFα. Heightened TIGAR expression was observed in GBM tumors. While NCS induced ATM phosphorylation in a NFκB independent manner, ATM inhibition abrogated TIGAR and NFκB activation. Metabolic gene profiling indicated that TNFα affects NCS-mediated regulation of several genes associated with glycolysis. The existence of ATM-NFκB axis that regulate metabolic modeler TIGAR to overcome prosurvival response in NCS and TNFα cotreated cells, suggests mechanisms through which inflammation could affect resistance and adaptation to radiomimetics despite concurrent induction of death. 相似文献