There are evidences indicating that cysteine proteases play an essential role in malaria parasites;therefore, an obvious area of investigation is the inhibition of these enzymes to treat malaria. Small cysteine protea...There are evidences indicating that cysteine proteases play an essential role in malaria parasites;therefore, an obvious area of investigation is the inhibition of these enzymes to treat malaria. Small cysteine protease inhibitors of malaria are well studied, but macromolecular nature of inhibitor is a new field to explore. In malarial cysteine proteases, there are macromolecular endogenous inhibitors playing important roles in regulation of the cysteine protease activity of parasite and host. Recent studies suggested that there are known and characterized endogenous inhibitors like falstatin present in P. falciparum, PbICP (inhibitor of cysteine protease in P. berghei), PyICP (inhibitor of cysteine protease in P. yoelli), and other macromolecular inhibitors which are the prodomain of enzyme itself regulating the activity of the mature enzyme. All the known macromolecular endogenous inhibitors are using specific loop-like structure to interact with malarial cysteine proteases. The majority of macromolecular inhibitors are competitive in nature, and block access to the active site of their target protease, but do not bind in a strictly substrate-like manner. They rather interact with the protease subsites and catalytic residues in a non-catalytically competent manner. In future, designing inhibitors based on these protein-protein interactions will be a new approach in the field of malaria. Since macromolecular inhibitors can gain potency through the burial of a large surface area and specificity through contacts with secondary binding sites critical for inhibition, and could be less prone to drug resistant mutation.展开更多
研究大豆分离蛋白(soy protein isolate,SPI)-葡聚糖共价接枝物的制备及其乳化性质和作为姜黄素载体的性能。在95℃的"大分子拥挤"体系条件下,2种大分子通过美拉德反应进行共价接枝。根据糖基化产物在SPI等电点附近(p H 4.5)...研究大豆分离蛋白(soy protein isolate,SPI)-葡聚糖共价接枝物的制备及其乳化性质和作为姜黄素载体的性能。在95℃的"大分子拥挤"体系条件下,2种大分子通过美拉德反应进行共价接枝。根据糖基化产物在SPI等电点附近(p H 4.5)和中性(p H 6.5)条件下的溶解性将其分成2个组分,分别为MC45和MC65,并对其性能表征分析。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和分子质量测定分析显示,反应后生成大分子质量的接枝物。MC45制备的乳液在酸性环境中的粒度低于MC65,其平均粒径约为10μm,并且受离子浓度和温度的影响较小。与天然蛋白、SPI-葡聚糖混合物及MC45相比,荷载量、1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl,DPPH)自由基清除率分析表明MC65组分具有更好的姜黄素运载性能,MC65组分制备的姜黄素纳米颗粒荷载量为30.21μg/mg,DPPH自由基清除率为18.33%,其粒径最大。展开更多
文摘There are evidences indicating that cysteine proteases play an essential role in malaria parasites;therefore, an obvious area of investigation is the inhibition of these enzymes to treat malaria. Small cysteine protease inhibitors of malaria are well studied, but macromolecular nature of inhibitor is a new field to explore. In malarial cysteine proteases, there are macromolecular endogenous inhibitors playing important roles in regulation of the cysteine protease activity of parasite and host. Recent studies suggested that there are known and characterized endogenous inhibitors like falstatin present in P. falciparum, PbICP (inhibitor of cysteine protease in P. berghei), PyICP (inhibitor of cysteine protease in P. yoelli), and other macromolecular inhibitors which are the prodomain of enzyme itself regulating the activity of the mature enzyme. All the known macromolecular endogenous inhibitors are using specific loop-like structure to interact with malarial cysteine proteases. The majority of macromolecular inhibitors are competitive in nature, and block access to the active site of their target protease, but do not bind in a strictly substrate-like manner. They rather interact with the protease subsites and catalytic residues in a non-catalytically competent manner. In future, designing inhibitors based on these protein-protein interactions will be a new approach in the field of malaria. Since macromolecular inhibitors can gain potency through the burial of a large surface area and specificity through contacts with secondary binding sites critical for inhibition, and could be less prone to drug resistant mutation.
文摘研究大豆分离蛋白(soy protein isolate,SPI)-葡聚糖共价接枝物的制备及其乳化性质和作为姜黄素载体的性能。在95℃的"大分子拥挤"体系条件下,2种大分子通过美拉德反应进行共价接枝。根据糖基化产物在SPI等电点附近(p H 4.5)和中性(p H 6.5)条件下的溶解性将其分成2个组分,分别为MC45和MC65,并对其性能表征分析。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和分子质量测定分析显示,反应后生成大分子质量的接枝物。MC45制备的乳液在酸性环境中的粒度低于MC65,其平均粒径约为10μm,并且受离子浓度和温度的影响较小。与天然蛋白、SPI-葡聚糖混合物及MC45相比,荷载量、1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl,DPPH)自由基清除率分析表明MC65组分具有更好的姜黄素运载性能,MC65组分制备的姜黄素纳米颗粒荷载量为30.21μg/mg,DPPH自由基清除率为18.33%,其粒径最大。
