基于“底物包膜”假说筛选新型HIV-1蛋白酶抑制剂

基于“底物包膜”假说, 以现有HIV-1蛋白酶抑制剂Darunavir为模板构建药效团模型并对中药化学数据库进行搜索; 采用分子对接方法进一步考察化合物与HIV-1蛋白酶结合情况及其与“底物包膜”符合程度, 优先选出两个化合物Annomonicin和去乙酰蟾蜍它灵; 应用分子动力学方法对这两个化合物进行动力学模拟, 观察它们与蛋白酶结合的复合物在动力学过程中的稳定性并计算其结合自由能, 综合评价筛选结果, 最终确定化合物Annomonicin具有更潜在的深入研究价值.     

Design, Synthesis and Molecular Docking of a Novel Small-molecule Inhibitor of Caspase-3

4,5-Dihydro-3-methylbenzo[1,2-b]furan-4,5-dione(4) was identified as a novel and potent inhibitor of caspase-3 through structural modification of an existing drug,sodium tanshinone ⅡA sulfonate(STS).Compound 4 showed high potency against caspase-3 in vitro(IC50=0.13 μmol/L).Molecular docking study further provided an insight into the interaction of compound 4 with activated caspase-3.Hence,this small-molecule caspase-3 inhibitor could be a promising therapeutic candidate against diseases caused by abnormally up-regulated apoptosis.     

A Study on Inhibitors for the Prevention of Hydrate Formation in Gas Transmission Pipeline

Gas Hydrate is usually formed during the transportation and treatment of oil and gas, resulting in the plugging of gas pipeline and equipment. Three thermodynamic calculation formulas are analyzed to deal with this problem. The lowering of the freezing point of the inhibitors AT is used to calculate the formation temperature of natural gas hydrates. This is considered to be a good approach because it is not limited by what kind and what concentration of inhibitors one uses. Besides, the rate of lowering of the freezing point could be easily measured. The result of testing methanol and mono-ethylene glycol in a reactor shows that adding 10% inhibitors to the reactor can prevent the hydrates formation. Kinetic inhibitors are favored in the present research. They are divided into two types, polymer and surface-active agents. Their characteristics, mechanisms, and application prospect are separately discussed. Polymer inhibitors exhibit better efficiency. The result of field application of VC-713 inhibiter is also given in this article. In practice, the combination of thermodynamic inhibitors and kinetic inhibitors gives better result.     

化学修饰的寡核苷酸: 合成、性质和应用

本文综述了近年来化学修饰的寡核苷酸研究的进展,介绍了化学修饰的寡核苷酸的种类, 化学合成方法, 生物作用原理及应用方面已达到的成継34This review deals with the progress in the research of chemically modified oligonucleotides: the synthesis, the chemical and biological properties and the potential applications as a new research tool and new therapeutic approach.     

α-羟乙基过氧自由基的自身衰变及其与槲皮素和邻苯二酚反应的脉冲辐解动力学研究

脂质过氧化反应是人体内很多病理现象的原因 ,而槲皮素是一种很强的过氧化反应抑制剂 .本文选择α-羟乙基过氧自由基作为脂质过氧自由基的模拟物 ,研究了其与槲皮素和邻苯二酚的反应动力学 .首次得到纯乙醇体系中 α-羟乙基自由基的一级和二级自身衰变速率常数分别为 (4 0 .4± 2 .6) s- 1和 (6.9± 0 .9)×1 0 8mol- 1·L· s- 1 .用脉冲辐解方法得到槲皮素与 α-羟乙基过氧自由基反应的速率常数为 (2 .1± 0 .3 )× 1 0 7mol- 1·L· s- 1 .同时选择邻苯二酚作为多酚化合物的模型化合物 ,用脉冲辐解法研究了其与 α-羟乙基过氧自由基的反应 .得到邻苯二酚与α-羟乙基过氧自由基反应的速率常数为 (3 .1± 0 .1 )× 1 0 5mol- 1 · L· s     

Corrosion Inhibition of a Green Scale Inhibitor Polyepoxysuccinic Acid

The corrosion inhibition of a green scale inhibitor, polyepoxysuccinic acid (PESA) was studied based on dynamic tests. It is found that when PESA is used alone, it had good corrosion inhibition. So, PESA should be included in the category of corrosion inhibitors. It is not only a kind of green scale inhibitor, but also a green corrosion inhibitor. The synergistic effect betweenPESA and Zn2 or sodium gluconate is poor. However, the synergistic effect among PESA, Zn2 and sodium gluconate is excellent, and the corrosion inhibition efficiency for carbon steel is higher than 99%. Further study of corrosion inhibition mechanism reveals that corrosion inhibition of PESA is not affected by carboxyl group, but by the oxygen atom inserted. The existence of oxygen atom in PESA molecular structure makes it easy to form stable chelate with pentacyclic     

2-氰基-3-取代吡啶甲胺基-3-取代丙烯酸乙氧乙酯的合成和除草活性研究

一系列2-氰基-3-取代吡啶甲胺基丙烯酸酯被合成作为光合作用光系统II电子传递抑制剂. 生测发现一些目标化合物表现出很好的除草活性, 如(Z)-2-氰基-3-异丙基-3-(2-烷氧基取代的吡啶-3-基)甲胺基丙烯酸乙氧乙酯. 生测结果表明在吡啶环的2位合适的取代基和丙烯酸酯的3位取代基的体积对除草活性至关重要.     

糖原合成酶激酶抑制剂模型的建立

选取四类共89种活性较高的糖原合成酶激酶（GSK-3）抑制剂作为分子训练集，利用CATALYST系统，经构象分析，分子叠合等过程构建出药效团模型。筛选出具有一个氢键受体，一个芳香疏水中心，两个环芳香性的药效团模型 (weight=2.4,RMS=0.50, null cost- fixed cost =104, correlation coefficient=0.95)。该模型具有较强的预测活性能力，可用于优化分子结构，找到高效低毒的化合物。     

天然及修饰型天花粉多肽类胰蛋白酶抑制剂的研究

本文用固相Anhydro-胰蛋白酶亲和层析和HPLC C_(18)柱反相层析等方法,从中草药天花粉中分离纯化了一多肽类胰蛋白酶抑制剂,它有两个主要组份,均含有27个氨基酸残基,其中包括3对二硫键,经顺序测定表明,两者的区别仅限于第九位的残基不同,分别为Lys及Gln。此抑制剂活性中心Arg-Ile(3,4)的肽键在低pH下极易被胰蛋白酶“修饰”而断裂。这是迄今为止已知的天然蛋白质抑制剂中最小的胰蛋白酶抑制剂。胰蛋白酶对天花粉抑制剂的修饰作用类似酶对底物的酶促反应。“修饰”型的天花粉抑制剂其与胰蛋白酶的解离常数约是天然抑制剂的4倍。