Triazolo-fused 3＇,4＇-cyclic nucleoside 4＇-spiro nucleoside analogues were synthesized by an intramolecular 1,3-dipolar cycloaddition of 4＇-azido nucleoside derived azido-alkynes in a regio- and stereo-specific man...Triazolo-fused 3＇,4＇-cyclic nucleoside 4＇-spiro nucleoside analogues were synthesized by an intramolecular 1,3-dipolar cycloaddition of 4＇-azido nucleoside derived azido-alkynes in a regio- and stereo-specific manner. The thy- mine nucleoside base in these target compounds was transformed into the corresponding 5-methyl cytosine component. The synthesized compounds were examined in an MAGI（multinuclear-activation galactosidase indicator） assay for exploring the anti-HIV activity and in a H9 T（human T lymphocytes Hg） assay for measuring the cell toxicity.展开更多
AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
Cyclopropanedicarboxylic anhydride can be converted to 4-substituted (or 4-spiro-)3-oxabicyclo[3.1.0]hexan-2-one by addition of Grignard (or α,ω-di-Crignard) reagents in ether or tetrahydrofuran solution.
Promoted and mediated by an ionic liquid-[bmim][BF4], fused pyrans or arylbis（4-hydroxy-6-methyl-2-oxo-2H-pyran-3- yl）methanes were efficiently and selectively prepared from the reaction of aldehyde and 4-hydroxy-6-...Promoted and mediated by an ionic liquid-[bmim][BF4], fused pyrans or arylbis（4-hydroxy-6-methyl-2-oxo-2H-pyran-3- yl）methanes were efficiently and selectively prepared from the reaction of aldehyde and 4-hydroxy-6-methyl-2-oxo-pyran with or without acetic anhydride. By using these novel procedures, pyrimidine nucleoside-fused pyran and arylbis（pyranon-3-yl）methane hybrids with potential biological activities were constructed.展开更多
AIM： To investigate the safety of β-L-D4A on DNA polymerase α.METHODS： Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were de...AIM： To investigate the safety of β-L-D4A on DNA polymerase α.METHODS： Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymeraseα . RESULTS： DNA polymerase was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant （Km = 3.22 i^mol/L）, 50% inhibition concentration （IC50 = 178.49 μmol/L） and inhibition constant （Ki = 126 mol/L） of β-L-D4A were determined by kinetic analysis. CONCLUSION： β-L-D4A is a more safe nucleoside for hepatitis B virus （HBV） infection with a lower host toxicity.展开更多
Pancreatic ductal adenocarcinoma(PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified...Pancreatic ductal adenocarcinoma(PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.展开更多
文摘Triazolo-fused 3＇,4＇-cyclic nucleoside 4＇-spiro nucleoside analogues were synthesized by an intramolecular 1,3-dipolar cycloaddition of 4＇-azido nucleoside derived azido-alkynes in a regio- and stereo-specific manner. The thy- mine nucleoside base in these target compounds was transformed into the corresponding 5-methyl cytosine component. The synthesized compounds were examined in an MAGI（multinuclear-activation galactosidase indicator） assay for exploring the anti-HIV activity and in a H9 T（human T lymphocytes Hg） assay for measuring the cell toxicity.
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
文摘Cyclopropanedicarboxylic anhydride can be converted to 4-substituted (or 4-spiro-)3-oxabicyclo[3.1.0]hexan-2-one by addition of Grignard (or α,ω-di-Crignard) reagents in ether or tetrahydrofuran solution.
基金the National Natural Science Foundation of China(No.20772025)the Program for Science & Technology Innovation Talents in Universities of Henan Province(No.2008HASTIT006)the Natural Science Foundation of Department of Education of Henan Province(No.2008A150013).
文摘Promoted and mediated by an ionic liquid-[bmim][BF4], fused pyrans or arylbis（4-hydroxy-6-methyl-2-oxo-2H-pyran-3- yl）methanes were efficiently and selectively prepared from the reaction of aldehyde and 4-hydroxy-6-methyl-2-oxo-pyran with or without acetic anhydride. By using these novel procedures, pyrimidine nucleoside-fused pyran and arylbis（pyranon-3-yl）methane hybrids with potential biological activities were constructed.
基金National Natural Science Foundation of China,No.30330680
文摘AIM： To investigate the safety of β-L-D4A on DNA polymerase α.METHODS： Ion exchange chromatography was used to separate DNA polymerase cc from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymeraseα . RESULTS： DNA polymerase was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant （Km = 3.22 i^mol/L）, 50% inhibition concentration （IC50 = 178.49 μmol/L） and inhibition constant （Ki = 126 mol/L） of β-L-D4A were determined by kinetic analysis. CONCLUSION： β-L-D4A is a more safe nucleoside for hepatitis B virus （HBV） infection with a lower host toxicity.
文摘Pancreatic ductal adenocarcinoma(PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.
文摘目的:采用高效液相色谱-质谱联用技术鉴定艾滋病治疗药物去羟肌苷的有关物质结构。方法:Inert Surstain C_(18)(250 mm×4.6 mm,5μm)色谱柱,以0.386%醋酸铵溶液加氨水调节p H至8.0为流动相A,以甲醇-乙腈(50∶50)为流动相B,进行梯度洗脱,电喷雾正离子化高分辨TOF/MS和MS/MS检测并解析有关物质结构。TOF/MS雾化气压力345 k Pa,温度350℃,干燥气流量10 L·min^(-1),毛细管电压4 k V,碎片电压100 V,MS/MS测定氩气CID压力0.2 Pa,碰撞能量25 e V。结果:检测到去羟肌苷原料中共有8个有关物质,通过有机反应机制分析和质谱解析鉴定了他们的结构,他们分别是9-(2-氧基-丁酸)-1,4,5,7,8,9-六氢-嘌呤-6-酮、次黄嘌呤、肌苷、2′-去氧肌苷、9-(2-羟基-乙酰基)-1,9-双氢-嘌呤-6-酮、3′-去氧肌苷、2′,3′-脱水肌苷、9-(2-羟乙基-4-丙酸甲酯-四氢呋喃)-1,9-双氢-6H-嘌呤-6-酮。结论:采用色谱-质谱联用技术能有效地鉴定去羟肌苷的有关物质,可为其质量控制研究提供参考。
