The chiral separations of four pharmaceutical racemates which contain N-alkyl groups were satisfactorily resolved using SBE-β-CD as a chiral mobile phase additive （CMPA） in a RP-HPLC system （the resolution is 2.70...The chiral separations of four pharmaceutical racemates which contain N-alkyl groups were satisfactorily resolved using SBE-β-CD as a chiral mobile phase additive （CMPA） in a RP-HPLC system （the resolution is 2.701 for ondansetron hydrochloride, 1.996 for sulpiride, 1.293 for clenbuterol hydrochloride and 0.816 for omeprazole）. In addition, the effects of different parameters such as CD type and CD concentration were investigated. The separation mechanism arises through the combination of several potential interactions, including electrostatic interactions as well as hydrogen bonding interactions and hydrophobic inclusion interactions, which allow for the SBE-β-CD-drug complexation with strong stereoselectivity and stability. The resolution also relates to the number and location of N atoms in the enantiomers. This method will be applicable to the isolation of various types of biologically imoortant enantiomers containing N-alkyl groups.展开更多
In this work,a novel kind of particulate capillary precolumns with double-end polymer monolithic frits has been developed.Firstly,the polymer monolithic frit at one end was prepared via photo-initiated polymerization ...In this work,a novel kind of particulate capillary precolumns with double-end polymer monolithic frits has been developed.Firstly,the polymer monolithic frit at one end was prepared via photo-initiated polymerization of a mixture of lauryl methacrylate and ethyleneglycol dimethacrylate with 1-propanol and 1,4-butanediol as porogens and 2,2-dimethoxy-2-phenylacetophenone as a photo-initiator in UV transparent coating capillary（100 μm i.d.）.Subsequently,C18 particles（5 μm,100 A） were packed into the capillary,and sealed with the polymer monolithic frit at another end.To prevent the reaction of monomers and C18 particles,the packed C18 particles were masked during UV exposure.The loading capacity of such a precolumn was determined to be about 9 μg by frontal analysis with a synthetic peptide APGDR1 YVHPF as a model sample.Furthermore,two parallel precolumns were incorporated into a two-dimensional nano-liquid chromatography（2D nano-LC） system with dual capillary trap columns for peptide trapping and concentration.Compared to 2D nano-LC system with a single trap column,such two dimensional separations could be operated simultaneously to improve the analysis throughput.All these results demonstrated that such capillary precolumns with double frits would be promising for high-throughput proteome analysis.展开更多
Thermoresponsive poly（N-isopropylacrylamide） （PNIPAAm） brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymeriza- tion （SI-ATRP）. The grafting reaction started from ...Thermoresponsive poly（N-isopropylacrylamide） （PNIPAAm） brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymeriza- tion （SI-ATRP）. The grafting reaction started from the surfaces of 2-bromoisobutyrate- functionalized silica particles in 2-propanol aqueous solution at ambient temperature using CuCIICuCI21N, N,N＇,N＇,N”.pentamethyldiethylenetriamine （PMDETA） as the catalytic system. Based on thermogravimetric analysis （TGA） results, the grafting amount and grafting density of PNIPAM chains on the surface of silica were calculated to be 1.29 mg/ m^2 and 0.0215 chains/nm^2, respectively. The gel permeation chromatography （GPC） result showed the relatively narrow molecular weight distribution （MwlMn= 1.21） of the grafted PNIPAAm. The modified silica particles were applied as high-performance liquid chromatography （HPLC） packing materials to successfully separate three aromatic compounds using water as mobile phase by changing column temperature. Temperature- dependent hydrophilic/hydrophobic property alteration of PNIPAAm brushes grafted on silica particles was determined with chromatographic interaction between stationary phase and analytes. Retention time was prolonged and resolution was improved with increasing temperature. Baseline separation with high resolution at relatively low temperatures was observed, demonstrating dense PNIPAAm brushes were grafted on silica surfaces.展开更多
Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma(HCC)patients.However,the precise mechanism of resistance to sorafenib remains unclear.Therefore,to obtain a de...Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma(HCC)patients.However,the precise mechanism of resistance to sorafenib remains unclear.Therefore,to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeutic targets are very important for improving the clinical prognosis of HCC patients.In this study,a label-free quantitative proteomics method was performed to investigate the proteins differentially expressed between HepG2 and the sorafenib-acquired resistance HepG2(HepG2-R)cells.In total,84 differential expressed proteins were identified between the two cell lines.Bioinformatics analysis results demonstrated the dysregulated metabolic processes have a significant impact on the drug resistance of HepG2-R cells.Among them,the expression of Microsomal glutathione S-transferase 1(MGST1)in two cell lines was further confirmed by western blot method.Moreover,colony formation assay and trypan blue dye assay results revealed that MGST1 is closely connected with the sorafenib resistance of HepG2-R cells,and the knockdown of MGST1 increased the sensitivity of sorafenib resistance HepG2-R cells to sorafenib treatment.In conclusion,these results lay a foundation for deciphering the mechanism for HCC sorafenib resistance and present a possibility of MGST1 serving as a therapeutic target for the treatment of sorafenib resistance HCC.展开更多
基金supported by the National Science and Technology Special Projects(Nos.2012ZX 09301-002-001 and 2012 ZX09301-002-006)the Research and Application of New Efficient Analytical Technologies and Methods in Drug Quality Control and Drug Safety(No.2011IM030200)the State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Open Project(No.GTZK201310)
文摘The chiral separations of four pharmaceutical racemates which contain N-alkyl groups were satisfactorily resolved using SBE-β-CD as a chiral mobile phase additive （CMPA） in a RP-HPLC system （the resolution is 2.701 for ondansetron hydrochloride, 1.996 for sulpiride, 1.293 for clenbuterol hydrochloride and 0.816 for omeprazole）. In addition, the effects of different parameters such as CD type and CD concentration were investigated. The separation mechanism arises through the combination of several potential interactions, including electrostatic interactions as well as hydrogen bonding interactions and hydrophobic inclusion interactions, which allow for the SBE-β-CD-drug complexation with strong stereoselectivity and stability. The resolution also relates to the number and location of N atoms in the enantiomers. This method will be applicable to the isolation of various types of biologically imoortant enantiomers containing N-alkyl groups.
基金the financial support from National Basic Research Program of China(No.2012CB910604)National Natural Science Foundation of China(No.20935004)+1 种基金the Creative Research Group Project by NSFC(No.21321064)National High Technology Research and Development Program of China (No.2012AA020202)
文摘In this work,a novel kind of particulate capillary precolumns with double-end polymer monolithic frits has been developed.Firstly,the polymer monolithic frit at one end was prepared via photo-initiated polymerization of a mixture of lauryl methacrylate and ethyleneglycol dimethacrylate with 1-propanol and 1,4-butanediol as porogens and 2,2-dimethoxy-2-phenylacetophenone as a photo-initiator in UV transparent coating capillary（100 μm i.d.）.Subsequently,C18 particles（5 μm,100 A） were packed into the capillary,and sealed with the polymer monolithic frit at another end.To prevent the reaction of monomers and C18 particles,the packed C18 particles were masked during UV exposure.The loading capacity of such a precolumn was determined to be about 9 μg by frontal analysis with a synthetic peptide APGDR1 YVHPF as a model sample.Furthermore,two parallel precolumns were incorporated into a two-dimensional nano-liquid chromatography（2D nano-LC） system with dual capillary trap columns for peptide trapping and concentration.Compared to 2D nano-LC system with a single trap column,such two dimensional separations could be operated simultaneously to improve the analysis throughput.All these results demonstrated that such capillary precolumns with double frits would be promising for high-throughput proteome analysis.
文摘Thermoresponsive poly（N-isopropylacrylamide） （PNIPAAm） brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymeriza- tion （SI-ATRP）. The grafting reaction started from the surfaces of 2-bromoisobutyrate- functionalized silica particles in 2-propanol aqueous solution at ambient temperature using CuCIICuCI21N, N,N＇,N＇,N”.pentamethyldiethylenetriamine （PMDETA） as the catalytic system. Based on thermogravimetric analysis （TGA） results, the grafting amount and grafting density of PNIPAM chains on the surface of silica were calculated to be 1.29 mg/ m^2 and 0.0215 chains/nm^2, respectively. The gel permeation chromatography （GPC） result showed the relatively narrow molecular weight distribution （MwlMn= 1.21） of the grafted PNIPAAm. The modified silica particles were applied as high-performance liquid chromatography （HPLC） packing materials to successfully separate three aromatic compounds using water as mobile phase by changing column temperature. Temperature- dependent hydrophilic/hydrophobic property alteration of PNIPAAm brushes grafted on silica particles was determined with chromatographic interaction between stationary phase and analytes. Retention time was prolonged and resolution was improved with increasing temperature. Baseline separation with high resolution at relatively low temperatures was observed, demonstrating dense PNIPAAm brushes were grafted on silica surfaces.
基金supported by grants from National Natural Science Foundation(21725506,32071434)National Key Research and Development Program of China(2016YFA0501401)
文摘Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma(HCC)patients.However,the precise mechanism of resistance to sorafenib remains unclear.Therefore,to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeutic targets are very important for improving the clinical prognosis of HCC patients.In this study,a label-free quantitative proteomics method was performed to investigate the proteins differentially expressed between HepG2 and the sorafenib-acquired resistance HepG2(HepG2-R)cells.In total,84 differential expressed proteins were identified between the two cell lines.Bioinformatics analysis results demonstrated the dysregulated metabolic processes have a significant impact on the drug resistance of HepG2-R cells.Among them,the expression of Microsomal glutathione S-transferase 1(MGST1)in two cell lines was further confirmed by western blot method.Moreover,colony formation assay and trypan blue dye assay results revealed that MGST1 is closely connected with the sorafenib resistance of HepG2-R cells,and the knockdown of MGST1 increased the sensitivity of sorafenib resistance HepG2-R cells to sorafenib treatment.In conclusion,these results lay a foundation for deciphering the mechanism for HCC sorafenib resistance and present a possibility of MGST1 serving as a therapeutic target for the treatment of sorafenib resistance HCC.
