多糖硫酸化修饰和多糖硫酸酯的研究进展

硫酸多糖是一类糖羟基上带有硫酸根的多糖,包括从植物中提取的各种硫酸多糖、肝素、天然多糖的硫酸衍生物及人工合成的各种硫酸多糖。硫酸多糖具有抗病毒、抗肿瘤、抗凝血和增强免疫等生物活性,为提高中药多糖的生物活性,可通过硫酸化修饰的方法进行结构改造,获取多糖硫酸酯。本文就多糖的硫酸化修饰方法、多糖硫酸酯的生物学活性及其影响因素、作用机制和临床应用进行了综述。     

生物大分子体系及其相互作用的计算机模拟

生物大分子体系及其相互作用的计算机模拟陈凯先（中国科学院上海药物研究所２０００３１）随着分子生物学的发展和计算机技术的进步,运用各种数学、物理学的理论方法,以计算机作为工具进行生物学的基本理论研究,特别是进行生物大分子体系及其相互作用的计算机分子图形...     

生物大分子的类型

生物大分子是细胞的基本结构和功能单位,也是研究生命现象中的物质基础。生物体内的分子组成如何?哪些分子才算生物大分子?这些大分子有没有分子量的下限?     

原始生物大分子动态的数学模型及其进化意义

本文应用生态学上关于种群增长及种间竞争的逻辑斯缔方程,提出原始生物大分子动态的数学模型,对从该模型推导得的几种可能结果进行了分析,得出在生命起源初期的原始生物圈的生物多样性是很低的结论,即原始生物圈中较大量存在的只是一些种类单一的,可复制的原始生物大分子,因此,可以认为生物进化就是建立在这样的一个基础上,并沿着生物多样性不断提高的途径演化,该模型还有助于对广泛存在于现代生物基因组中的重复序列的起源的认识。     

生物大分子起源问题的讨论

关于生命在地球上的起源与进化问题,历来是一个颇多争论的学术领域。显然,人们无法目睹三十几亿年前地球上曾经发出的事情,也难以用实验的方法来重温这一漫长的历史过程,而只能凭借地球留给我们的某些蛛丝马迹去推想,去研究,去探索。伴随着科学技术的发展,有关生命起源的     

硫酸化对金顶侧耳多糖构象及生物活性的影响

从金顶侧耳子实体中分离纯化一半乳甘露聚糖ＰＣ－３。该多糖在水中为无规线团构象,与Ｃｏｎ Ａ可相互结合并产生沉淀,对柯萨奇病毒ＣＢ５有一定的抑制作用,ＰＣ－３经硫酸化修饰后,由于同性电荷的排斥作用,使糖链的无规线团扩展呈伸展状态,局部可能形成螺旋。硫酸化的ＰＣ－３与Ｃｏｎ Ａ不能结合成多糖－蛋白复合物,但显著地提高了抗病毒ＣＢ５的活性。     

斑马鱼蛋白酪氨酸硫酸化修饰的检测方法研究

蛋白酪氨酸硫酸化(protein tyrosine sulfation, PTS)是一种重要的翻译后修饰,调控生命活动中多种生理和病理过程,但由于PTS状态不稳定且目前缺乏有效的富集方法,因此在生物样品中难以进行有效地检测。本研究以模式动物斑马鱼(Danio rerio)为研究材料,利用Orbitrap Exploris 480高分辨质谱仪检测了斑马鱼胚胎发育早期总蛋白的酪氨酸硫酸化修饰水平,通过该方法共计检测到26种蛋白(包括膜蛋白、分泌蛋白、胞质蛋白和核蛋白等)存在潜在的29个酪氨酸硫酸化修饰位点。本研究建立了斑马鱼胚胎发育早期蛋白酪氨酸硫酸化修饰的检测方法,为探索生物体蛋白硫酸化修饰的作用机制奠定了技术基础。     

基于设计的生物大分子成药性优化策略研究进展

目前生物药物正处在高速发展阶段,但生物大分子的一些固有特性限制了其成药性,使得很多具有良好治疗潜能的生物大分子 最终不能开发成药物,因而严重制约了生物药物的发展。生物药物开发的瓶颈已从“新分子的产生”转向“如何获得具有优良生理特性 和预期治疗效果的有效药物”。近年来,通过合理设计改造生物大分子高级结构以优化其成药性的研究获得了快速发展。综述基于设计 的生物大分子成药性优化策略研究进展。     

生物大分子的非放射性标记

无论是克隆植物基因还是研究基因表达都离不开探针的标记和检测。历来所用的放射性同位素标记方法存在一些缺点。一是要预防核辐射对人体的损伤,操作不方便;二是为防止污染环境,必须谨慎地处置放射性废弃物;三是放射性标记的探针使用时间短,例如最常用的~(32)P半衰期仅14.3天,标记的探针要随时标记随时使用,放置不用则放射性随时间指数下降。为     

生物大分子相分离在植物中的研究进展

细胞中存在种类繁多的无膜细胞器,在感知环境信号,基因表达调控,RNA加工等过程中发挥了重要的作用,而生物大分子相分离被证明是无膜细胞器形成的主要方式。文章介绍了生物大分子相分离的概念与特征,总结了有关相分离在植物对环境信号响应中的研究进展,并对相分离在植物中的生物学功能进行了分类,以期解析相分离在植物生长发育和逆境适应中的作用机理,揭示植物无膜细胞器的本质与功能。     

黄酮的结构改造与生物活性

黄酮是一类重要的天然有机化合物,属于黄酮类化合物的一个亚类,具有广泛的生理活性,如抗肿瘤,抗炎,抗菌等.本文以化学修饰的黄酮衍生物为例,综述了具有抗多药耐药、抗肿瘤、抗菌等活性的黄酮衍生物结构与活性的关系.     

灰树花多糖的分子修饰及其活性研究进展

灰树花是一种高蛋白低脂肪的食品,具有免疫调节、抗氧化和抗肿瘤等生物活性。其中,多糖是灰树花的主要活性成分之一。对多糖进行分子修饰是提高它原有的生物活性或增加新活性的重要途径之一。综述了灰树花多糖的分子修饰方法,以及修饰后灰树花多糖的生物活性及其构效关系的研究进展,以期为灰树花多糖的深入研究和开发利用提供参考。     

基于生物大分子DNA的纳米硫化银的合成

利用DNA生物大分子为模板,硫代乙酰胺和硝酸盐为原料,制备出了颗粒状硫化银纳米结构体。同时采用琼脂糖电泳、FESEM、FTIR和XRD等多种表征手段对其结构组成进行了系统的分析,对其形成机理进行了探讨。     

分子印迹技术用于生物大分子的识别

分子印迹技术是一种人工合成具有分子识别功能的介质的一种新技术,近年来在许多领域都得到很大的发展。本文介绍了分子印迹技术的发展现状,尤其对生物大分子的分子印迹技术进行了详细论述,对生物大分子印迹采用的功能单体、印迹分子的种类、印迹的方法、印迹的机理、存在的问题和应用的前景等分别进行了讨论。     

Revelation of Antiviral Activities by Artificial Sulfation of a Glycosaminoglycan from a Marine Pseudomonas

Sulfated derivatives of a glycosaminoglycan containing l-glutamic acid produced by a marine Pseudomonas species, No. 42 strain, were prepared by the method of dicyclohexyl-carbodiimide-mediated reaction. Both low and high degrees of sulfation of the polysaccharides (products A1 and A2, respectively) were investigated for their antiviral activities against influenza virus type A (FluV-A) and B (FluV-B) in MDCK cells. Both preparations showed antiviral activity against FluV-A at the 50% antiviral effective concentration of 17.3 and 5.2 μg/ml, respectively, whereas they had no antiviral activity against FluV-B. No cytotoxicity of either product was noted against MDCK cells at the 50% cytotoxic concentration of 100 μg/ml. Received April 4, 1998; accepted July 24, 1998.     

Phytochemical and Biological Activities of Pseudocalymma elegans: A False Garlic

Evaluation of phytochemical constituents and antioxidant and antimicrobial activities of hexane (PELH), dichloromethane (PELDCM), ethyl acetate (PELEA), and MeOH (PELM) extracts of young leaves of Pseudocalymma elegans have been carried out. Moreover, extracts have also been explored for the presence of sulphur containing compounds, 1,2‐dithiolane ( 33 ), diallyl disulfide ( 35 ), 3‐vinyl‐1,2‐dithiacyclohex‐5‐ene ( 37 ), and diallyl trisulfide ( 38 ) responsible for the garlic like smell of P. elegans. All the extracts were found to be antioxidant and showed potent inhibition with IC₅₀ values of 0.168 ± 0.001, 0.128 ± 0.002, 0.221 ± 0.011, and 0.054 ± 0.001, respectively, as compared to standard drugs ascorbic acid (AA) and butylated hydroxytoluene (BHT). The ethyl acetate extract (PELE) showed excellent activities against few Gram‐positive and Gram‐negative bacteria and some fungi as compared with standard drug ceftriaxone (3rd generation cephalosporin) and nystatin, respectively. Chemical constituents of hexane, dichloromethane, and ethyl acetate extracts were identified by gas chromatography‐mass spectrometry and mass spectral library search. Over all 55 chemical constituents were first time identified from the leaves which included branched and n‐hydrocarbons, fatty acids, fatty acid methyl esters, fatty alcohols, terpenes, alkaloid, vitamins, glycosides, aromatic compounds, and sulfur containing compounds. Two known chemical constituents, ursolic acid ( 1 ) and β‐amyrin ( 2 ), were also purified for the first time from the MeOH extract. To elucidate the structures of these compounds, UV, IR, EI‐MS, ¹H‐ and ¹³C‐NMR spectroscopy were used.     

Syntheses and Biological Activities of Danicalipin A Derivatives

Synthesis of three derivatives of danicalipin A, tetrachloride, trisulfate and a fluorescent probe was achieved through Wittig reaction strategy. Toxicity of the derivatives against brine shrimp (Artemia salina) as also investigated to provide useful information for the biological activity; i) less chloride derivative showed similar toxicity to danicalipin A, ii) the amphiphilic property, a characteristic feature of danicalipin A, was crucial because trisulfate considerably decreased the toxicity and iii) fluorescent derivative kept brine shrimp toxicity of danicalipin A.     

Improved Biological Activities of Isoepoxypteryxin by Biotransformation

Isoepoxypteryxin is the major coumarin of a Japanese medicinal plant Angelica shikokiana. This research was designed to study the effect of structural changes through fungal biotransformation on the reported biological activities of isoepoxypteryxin. Among the tested microorganisms, only Cordyceps sinensis had enzymes that could catalyze the ester hydrolysis and the reductive cleavage of the epoxide ring of isoepoxypteryxin, separately, to give two more polar metabolites (+)‐cis‐khellactone ( P1 ) and a new coumarin derivative (+)‐cis‐3′‐[(2‐methyl‐3‐hydroxybutanoyl)oxy]‐4′‐acetoxy‐3′,4′‐dihydroseselin ( P2 ), respectively. The polar metabolite P2 showed stronger cytotoxicity and higher selectivity than isoepoxypteryxin. On the molecular level, P2 showed more in vitro inhibition of both tubulin polymerization and histone deacetylase 8 (HDAC8). Similarly, P2 showed more neuroprotection against amyloid beta fragment 1 – 42 (Aβ_{1 – 42})‐induced neurotoxicity in human neuroblastoma cells (SH‐SY5Y) and exhibited more inhibition of the in vitro aggregation of Aβ_{1 – 42}. Both metabolites showed stronger antiplatelet aggregation by increased inhibition of thromboxane‐A2 synthase (TXS) activity and thromboxane‐A2 (TXA2) production. This study is the first to describe the improved cytotoxic, neuroprotective, and antiplatelet aggregation activities of isoepoxypteryxin through its biotransformation by C. sinensis.     

Effect of Sulfated Modification on the Molecular Characteristics and Biological Activities of Polysaccharides from Hypsizigus marmoreus

The effect of sulfated modification on polysaccharides from Hypsizigus marmoreus was examined by determining their molecular structures and bioactivities. The sulfation, which was implemented by using an orthogonal array design, produced polysaccharides with varying degrees of substitution (DS) ranging from 0.11 to 1.06. The sulfated polysaccharides exhibited a lower average molecular weight (M _w) and considerably higher radius of gyration (R _g) than those of native polysaccharide, suggesting that the conformation of the sulfated polysaccharides had been changed towards a more extended type. The inhibitory activity toward cancer cell growth was enhanced by treating with the sulfated polysaccharides by up to 34%, as compared to the native polysaccharide. In addition, treating with the sulfated polysaccharides increased the nitric oxide (NO) and cytokine (IL-1β and TNF-α) release to levels comparable to those detected in the positive control, lipopolysaccharide (LPS), suggesting that the sulfated polysaccharides might have strong immunomodulatory activity.     

Biological transformations of steroidal compounds: A review

Microbial transformation is an important tool for structural modification of organic compounds, especially natural products with complex structures like steroids. It can be used to synthesize chemical structures that are difficult to obtain by ordinary methods and as a model of mammalian metabolism due to similarity between mammalian and microbial enzyme systems. During recent years research has been focused on the structural modifications of bioactive steroids by using various microorganisms, in order to obtain biologically potent compounds with diverse structures. Steroidal compounds are responsible for important biological functions in the cells and manifest a variety of activities. This article covers the microbial transformation of sterols, steroidal hormones and some new types of steroids known as bufadienolides. Emphasis has placed on reporting metabolites that may be of general interest and on the practical aspects of work in the field of microbial transformations. The review covers the literature from 1994 to 2011.