越南槐根的抗HIV活性成分研究

为研究越南槐(Sophora tonkinensis)根的抗HIV蛋白酶活性成分及其分子对接机制,采用硅胶、MCI、Sephadex LH-20等多种色谱分离方法,对越南槐根的化学成分进行分离,采用HIV蛋白酶对化合物进行体外抗HIV活性筛选,运用分子对接手段初步探究活性化合物与HIV-1蛋白酶的结合机制。结果表明,从越南槐中共分离得到8个化合物,根据波谱数据分别鉴定为三叶豆紫檀苷(1)、苦参碱(2)、N-acetylnicotinamide (3)、2′-O-甲基腺苷(4)、毛蕊异黄酮苷(5)、玫瑰花苷(6)、环广豆根素(7)、芒柄花苷(8),此外还分离得到塑化剂衍生物邻苯二甲酸二(2-乙基)己酯(9)和邻苯二甲酸二异丁酯(10)。抗HIV蛋白酶活性测试显示化合物1和2的IC50分别为13.2和38.6μg/m L,分子对接表明其与HIV蛋白酶有一定的结合作用。化合物3～5为首次从该植物中分离得到,化合物1和2显示中等的抗HIV蛋白酶活性。     

多糖抗病毒作用研究进展Ⅱ.硫酸多糖抗病毒作用

硫酸多糖的抗病毒活性,包括抗艾滋病毒HIV1活性,在近年得以阐明。本文综述了硫酸多糖的抗病毒作用、抗病毒机理及其构效关系。硫酸多糖具有广阔的临床应用前景,其抗病毒作用值得深入研究。     

天然药物中抗HIV活性成分研究进展

天然产物往往具有独特的化学结构,是发现新药或药物先导物的重要途径之一.目前,从天然药物中发现了多种结构类型的具有抗HIV活性的化合物,如多糖类、生物碱类、香豆素类、黄酮类、木脂素类、醌类、酚酸类、萜类等,并且其作用机制并不局限于抑制逆转录酶或蛋白酶,可在HIV复制周期的各个环节发挥作用,本文按天然产物的结构类型进行归纳,综述了近年来源自天然药物的抗HIV活性成分研究进展,总结了的151个具有抗HIV活性的天然产物结构及其活性测试数据,以期为从天然化学成分中寻找、发现并研究开发有效的抗艾滋病药物提供线索.     

抗HIV—1活性的大环多胺类化合物与RNA的识别作用及其对细胞凋亡的影响

研究了具有抗HIV－1活性的大环多胺类化合物与RNA的识别作用,以及其对cos-7细胞凋亡的影响,以进一步探讨其抗HIV－1的作用机理。实验采用琼脂糖凝胶电泳方法。观察化合物与RNA的识别作用。通过流式细胞计数法探讨其对cos-7细胞凋亡的影响。运用计算机分子模型,从理论上Docking计算化合物与TAR RNA结合的可能性。结果表明,大环多胺类化合物MP－1、MP－2和MP－3不仅具有断裂RNA的作用,并可抑制Tat-RNA的相互作用,还可影响cos-7细胞亚二倍体的含量;理论化学计算数据与实验结果基本一致,这一结果提示合物的抗HIV－1活性可能通过作用于病毒基因组RNA而发挥作用,是多靶作用的结果。     

多糖修饰物及其抗肿瘤作用机制研究

多糖是指一类由十个以上单糖分子通过糖苷键连接而成的糖类物质,因其具有许多重要的生物学活性而备受关注,这其中最为突出的是其在抗肿瘤方面所表现出的效用。目前多糖抗肿瘤方面的主要研究课题集中在如何进一步提高多糖的抗肿瘤活性上。对多糖分子进行结构上的修饰能够使其抗肿瘤的活性得到一定程度地提高。本文对常见的多糖修饰方法,如硫酸化、羧甲基化、磷酸化、硒化、乙酰化等进行了总结,对经修饰后所得产物的抗肿瘤作用的不同机制进行了阐述,并对多糖化学修饰物的应用前景进行了展望,为未来多糖的开发与利用提供一定的理论依据。     

金樱子提取物中多糖的体外抗肿瘤活性研究

多糖是药用植物金樱子所含有的数种主要生物活性物质之一,其具有多种生物活性,厘清该成分的作用效应具有重要意义。本文通过将黔产金樱子制备为金樱子粉末、分离纯化得到活性成分金樱子多糖;采用磺酰罗丹明染色法测定其对人肝癌细胞BEL-7402以及人正常肝细胞HL-7702增殖的影响并比较。发现金樱子提取物中所存在的多糖类化合物对体外培养的人肝癌细胞BEL-7402的增殖具有一定抑制作用,其半数抑制浓度为(12.43±1.95)μmol/L;且对体外培养的人正常肝细胞HL-7702的毒性较低,其半数抑制浓度为(31.04±3.68)μmol/L。初步证明金樱子提取物中含有的多糖类化合物具有一定的体外抗肿瘤活性,作为低毒性的天然提取物,具有广阔的抗肿瘤前景。     

离子色谱在多糖疫苗及多糖蛋白结合疫苗质量控制中的应用

离子色谱具有方便、快速、灵敏度高、选择性好、重现性好、准确度高、可同时分析多种离子化合物等优点,其中的高效阴离子交换色谱-脉冲安培检测法(HPAEC-PAD)可直接分析糖类物质,可应用于多糖疫苗及多糖蛋白结合疫苗中多糖的分析。近年来,离子色谱应用在多糖及多糖蛋白结合疫苗的质量控制中,如测定疫苗中的多糖、游离糖、杂质多糖、对人有免疫原性的功能基团等的研究有许多报道,对有关内容进行了综述。     

法落海的化学成分及抗HIV活性(英文)

利用多种柱层析方法,从法落海(Angelica apaensis)95%乙醇提取物中分离得到8个化合物.经IR、MS、NMR等波谱数据鉴定为氧化前胡素(oxypeucedanin,1)、氧化前胡素水合物(oxypeucedanin hydrate,2)、异欧芹属乙素(isoimperatorin,3)、白当归脑(byakangelicin,4)、白当归素(byakangelicol,5)、3'-O-acetylhamaudol (6)、( )-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol(7)和9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate(8),其中,化合物6-8是首次从该植物中分离得到.我们对所有得到的8个化合物进行抗HIV活性分析,化合物1具有明显的抗HIV活性,其抑制合胞体形成的半数有效浓度(EC50)为1.6 ms/L,治疗指数(TI)为17.59.     

大戟属二萜类化学成分和生物活性研究进展

大戟属(Euphorbia)植物化学成分主要包括萜类、黄酮类、酚酸类等成分。该属植物具有抗肿瘤、抗炎、抗HIV等活性。本文主要综述了近十年来大戟属植物中发现的新的二萜类化合物及生物活性研究进展。     

多糖抗病毒作用研究进展Ⅲ.卡拉胶及其抗病毒作用

卡拉胶是源于某些红藻的天然硫酸多糖,具有多种生物活性。其显著的抗病毒活性,尤其是抗艾滋病HIV1活性,最近得以进一步证实。本文综述了卡拉胶的抗病毒作用,并展望其临床应用前景。     

Immunochemical studies on the capsular polysaccharides of pneumococcal type IX

1. In addition to the previously identified components, d-glucose, N-acetyl-d-glucosamine and d-glucuronic acid, the immunologically specific capsular polysaccharide of pneumococcal type IX (polysaccharide S IX) is now found to contain mannosamine and galactosamine, probably as their N-acetyl derivatives. 2. Partial hydrolysis yields a complex mixture of oligosaccharides, several of which have been separated. 3. One of these is alpha-d-glucuronopyranosyl-(1-->3)-d-glucose. It is an inhibitor of the precipitation of antipneumococcal type IX serum by polysaccharide S IX. 4. Two others, d-glucuronopyranosyl-(1-->3)-d-glucosamine and d-glucuronopyranosyl-(1-->3)-d-galactosamine have been identified and a trisaccharide and pentasaccharide partially characterized.     

人免疫缺陷病毒/艾滋病细胞免疫疫苗研究进展

由于人免疫缺陷病毒(HIV)具有变异快、亚型多、攻击免疫系统等特殊的生物学特点,HIV/艾滋病疫苗至今尚未研制成功。20多年来,艾滋病疫苗研究主要采用中和抗体为主和细胞免疫为主等两种策略,然而目前仍没有实质性突破。诱发广谱有效的强CD8+T细胞反应是研制有效HIV疫苗的重要策略。以次要保护性抗原为靶抗原、优化目的基因表达、多抗原联合使用策略,为研究HIV细胞免疫疫苗引入了新的思路。综合分析这些进展,对于重新思考艾滋病疫苗的研究策略可能会有所帮助。     

A radioimmunoprecipitation method in the serodiagnosis of HIV infection: the development of the optimal conditions for its performance and the evaluation of the possibilities for its use

The optimum conditions for using the method of radioimmunoprecipitation (RIP) for the detection of human immunodeficiency virus (HIV) in serum samples have been established. Out of several available cell lines persistently infected with HIV, specially selected line 17 has been chosen. The characteristic feature of this is the high and stable (under the conditions of prolonged cultivation) accumulation of virus-specific proteins in infected cells. The optimum conditions for making the test and its evaluation have also been established. The data of literature on the advantages of the method of RIP over such traditional methods as the enzyme immunoassay and immunoblotting have been confirmed. Thus, the presence of specific antibodies in several serum samples registered as false negative has been established. The intertypical reactivity of two serotypes of the virus, HIV-1 and HIV-2, has been studied. Cross reactivity of antibodies with respect to the HIV gene gag, but not with respect to viral glycoproteids, has been established. Ideas on the expediency and prospects of using RIP for the serological control of HIV infection are presented.     

Structure of a PL17 Family Alginate Lyase Demonstrates Functional Similarities among Exotype Depolymerases

Brown macroalgae represent an ideal source for complex polysaccharides that can be utilized as precursors for cellulosic biofuels. The lack of recalcitrant lignin components in macroalgae polysaccharide reserves provides a facile route for depolymerization of constituent polysaccharides into simple monosaccharides. The most abundant sugars in macroalgae are alginate, mannitol, and glucan, and although several classes of enzymes that can catabolize the latter two have been characterized, studies of alginate-depolymerizing enzymes have lagged. Here, we present several crystal structures of Alg17c from marine bacterium Saccharophagus degradans along with structure-function characterization of active site residues that are suggested to be involved in the exolytic mechanism of alginate depolymerization. This represents the first structural and biochemical characterization of a family 17 polysaccharide lyase enzyme. Despite the lack of appreciable sequence conservation, the structure and β-elimination mechanism for glycolytic bond cleavage by Alg17c are similar to those observed for family 15 polysaccharide lyases and other lyases. This work illuminates the evolutionary relationships among enzymes within this unexplored class of polysaccharide lyases and reinforces the notion of a structure-based hierarchy in the classification of these enzymes.     

Identification and properties of a sterol-binding polysaccharide isolated from Saccharomyces Cerevesiae

A sterol-solubilizing polysaccharide isolated from yeast has been described (Adams, B. G. and Parks L. W. (1967) Biochem. Biophys. Res. Commun. 28,490–494) which greatly simplifies the addition of sterolsto aqueous media. The polysaccharide has now been identified by gas-liquid chromatography and carbazole reactions as yeast cell wall mannan. The cell wall mannan has been purified and binding constants for several sterols have been determined. Binding of sterols is a biphasic function of mannan concentration and is independent of pH over a range of 5 to 8.     

Stereochemical aspects of the antigenic determinants of bacterial polysaccharides: the Rhodococcus equi capsular polysaccharides

The antigenic specificity of bacterial capsular polysaccharides has been extensively investigated. The origin of this specificity arises from the diversity of the oligosaccharide epitopes of the polysaccharide. Nuclear magnetic resonance spectroscopy provides a very powerful tool for probing the structure of the oligosaccharide epitopes. Using this technique in conjunction with chemical methods, the structures of the serotype-specific capsular polysaccharide antigens of Rhodococcus equi have been investigated. These studies have led to the identification of several structural features which can be related to serologic type specificity. This review will focus on some stereochemical aspects of the antigen determinants. Nuclear magnetic resonance based methods for determination of bacterial polysaccharide primary structure and for stereochemical analysis of chiral acidic substituents are presented.     

Structural and Functional Comparison of Polysaccharide-Degrading Enzymes

Sugar molecules as well as enzymes degrading them are ubiquitously present in physiological systems, especially for vertebrates. Polysaccharides have at least two aspects to their function, one due to their mechanical properties and the second one involves multiple regulatory processes or interactions between molecules, cells, or extracellular space. Various bacteria exert exogenous pressures on their host organism to diversity glycans and their structures in order for the host organism to evade the destructive function of such microbes. Many bacterial organism produce glycan-degrading enzymes in order to facilitate their invasion of host tissues. Such polysaccharide degrading enzymes utilize mainly two modes of polysaccharide-degradation, a hydrolysis and a β-elimination process. The three-dimensional structures of several of these enzymes have been elucidated recently using X-ray crystallography. There are many common structural motifs among these enzymes, mainly the presence of an elongated cleft transversing these molecules which functions as a polysaccharide substrate binding site as well as the catalytic site for these enzymes. The detailed structural information obtained about these enzymes allowed formulation of proposed mechanisms of their action. The polysaccharide lyases utilize a proton acceptance and donation mechanism (PAD), whereas polysaccharide hydrolases use a direct double displacement (DD) mechanism to degrade their substrates.     

Structural and functional comparison of polysaccharide-degrading enzymes

Sugar molecules as well as enzymes degrading them are ubiquitously present in physiological systems, especially for vertebrates. Polysaccharides have at least two aspects to their function, one due to their mechanical properties and the second one involves multiple regulatory processes or interactions between molecules, cells, or extracellular space. Various bacteria exert exogenous pressures on their host organism to diversity glycans and their structures in order for the host organism to evade the destructive function of such microbes. Many bacterial organism produce glycan-degrading enzymes in order to facilitate their invasion of host tissues. Such polysaccharide degrading enzymes utilize mainly two modes of polysaccharide-degradation, a hydrolysis and a beta-elimination process. The three-dimensional structures of several of these enzymes have been elucidated recently using X-ray crystallography. There are many common structural motifs among these enzymes, mainly the presence of an elongated cleft transversing these molecules which functions as a polysaccharide substrate binding site as well as the catalytic site for these enzymes. The detailed structural information obtained about these enzymes allowed formulation of proposed mechanisms of their action. The polysaccharide lyases utilize a proton acceptance and donation mechanism (PAD), whereas polysaccharide hydrolases use a direct double displacement (DD) mechanism to degrade their substrates.     

Immunology of bacterial polysaccharide antigens

Carbohydrates in the form of capsular polysaccharides and/or lipopolysaccharides are the major components on the surface of bacteria. These molecules are important virulence factors in many bacteria isolated from infected persons. Immunity against these components confers protection against the disease. However, developing vaccines based on polysaccharides is difficult and several problems have to be solved. First of all, most of the bacterial polysaccharides are T-lymphocyte independent antigens. Anti-polysaccharide immune response is characterised by lack of T-lymphocyte memory, isotype restriction and delayed ontogeny. Children below 2 years of age and elderly respond poorly to polysaccharide antigens. Secondly, the wide structural heterogeneity among the polysaccharides within and between species is also a problem. Thirdly, some bacterial polysaccharides are poor immunogens in humans due to their structural similarities with glycolipids and glycoproteins present in man. The T-lymphocyte independent nature of a polysaccharide may be overcome by conjugating the native or depolymerised polysaccharide to a protein carrier. Such neoglycoconjugates have been proven to be efficient in inducing T-lymphocyte dependent immunity and to protect both infants as well as elderly from disease. Another approach to circumvent the T-lymphocyte independent property of polysaccharides is to select peptides mimicking the immunodominant structures. Several examples of such peptides have been described.