The production of ATE(anti-thrombus enzyme) from a kind of Bacillus subtilis immobilized in NaCS-PDMDAAC microcapsules was studied.The influence of mean diameter of microcapsules, concentration of PDMDAAC and the components of culture medium on the production of ATE in the condition of encapsulation culture was studied. In shaking flasks, the maximum enzyme activity in microcapsules was 1850 UK·ml -1 when the mean diameter of microcapsules was 1.60 mm, the concentration of PDMDAAC was 2.0% and the culture medium was LB culture medium(Tryptone)+glucose(0.5%)+phosphate buffer(100 ml).A bubbling culture system was designed. In this system, the maximum enzyme activity in microcapsules was 2050 UK·ml -1 , which was 3.6 times that in the condition of suspension fermentation; the maximum cell density in microcapsules was 4.89×10 9cells·ml -1 , which was 2.7 times that in the condition of suspension fermentation. 相似文献
The development of immunoproteasome-selective inhibitors is a promising strategy for treating hematologic malignancies, autoimmune and inflammatory diseases. In this context, we report the design, synthesis, and biological evaluation of a new series of amide derivatives as immunoproteasome inhibitors. Notably, the designed compounds act as noncovalent inhibitors, which might be a promising therapeutic option because of the lack of drawbacks and side effects associated with irreversible inhibition. Among the synthesized compounds, we identified a panel of active inhibitors with Ki values in the low micromolar or sub-micromolar ranges toward the β5i and/or β1i subunits of immunoproteasomes. One of the active compounds was shown to be the most potent and selective inhibitor with a Ki value of 21 nm against the single β1i subunit. Docking studies allowed us to determine the mode of binding of the molecules in the catalytic site of immunoproteasome subunits. 相似文献
CDC25 inhibition by thiazolopyrimidines : CDC25 is an attractive target for cancer therapy, as it is overexpressed in numerous cancers and is often associated with tumor aggressiveness and poor prognosis. Based on an in silico/in vitro screen, we developed a series of thiazolopyrimidines to further improve inhibitory activity and cytotoxic properties.
