生漆化学文摘

<正> 从三球悬铃木(Sycamore)细胞中分离得到的漆酶中,在N—连接的寡聚糖中,含有木糖的基本结构单元。 Takahashi,Noriko;Hotta,Taeko;et;Biochemiskry 1986,25(2),388-95(zng). 本文报道了由大槭树(Acer pseudoplatanus)细胞中分泌的漆酶的天冬氨酸—连接的寡聚糖结构。漆酶在寡聚糖糖蛋白酶的作用下可以得到糖蛋白肽,并可释放出一部分寡聚糖,这些被释放出的寡聚糖用凝胶进行过滤,再通过薄层层析及HPLC分级分离则     

透明质酸氧化降解的研究进展

低分子量透明质酸(LMWHA)和透明质酸寡聚糖(o-HA)具有抗氧化、免疫调节、促进伤口愈合、促血管生成和抗肿瘤等生物活性,透明质酸(HA)可以氧化降解为LMWHA和o-HA.对HA的氧化降解进行了综述.     

投产鉴定

新型寡聚糖生物农药通过鉴定 由中科院大连化物所承担的农业部“948”项目“系列寡聚糖生物农药及研究技术的引进”最近在大连通过了中科院组织的专家组验收和成果鉴定,一致认为,该项目研究成果已达到国际领先水平     

低聚木糖生产用木聚糖酶的选择性合成

以里氏木霉(Trichoderma reesei)Rut C-30为产酶菌,研究了碳源、碳氮比对木聚糖酶酶系组成的影响.低分子量组分较多的木聚糖有利于促进内切-β-木聚糖酶的合成,酶解产物中低聚木糖的含量较高(80.70%).低碳氮比有利于促进内切-β-木聚糖酶的合成,抑制外切-β-木糖苷酶的合成.以低分子量较多的木聚糖(7g/L)为碳源,降低培养基的碳氮比为4.0,调控培养60h,用该木聚糖酶酶解粗木聚糖,产物中低聚木糖占总糖的86.32%.     

糖芯片技术在生物医学中的应用及展望

化学糖生物学的研究成果在生物医药的研发领域日渐活跃,其中糖芯片技术(或称糖微阵列技术)在过去的15年间引起了科学家们的广泛关注。糖芯片技术通过将糖分子固定于芯片表面,然后利用荧光等信号检测糖分子和蛋白质或其他生物大分子的相互作用情况,从而分析凝集素和抗体的聚糖结合特性、检测细菌等病原体、诊断与鉴定疾病相关抗聚糖抗体等等。本文将从糖芯片的技术优势和其在生物医学领域的应用两个方面做简要介绍。     

双硫化魔芋寡糖素的合成

魔芋葡甘寡聚糖与二硫化碳和二甲胺进行双硫化加成反应制备了双硫化魔芋寡糖素（DS-OKGM）。魔芋葡甘寡聚糖与二硫化碳反应得到二硫代魔芋葡甘寡聚糖甲酸钠（SDFO）;二甲胺与二硫化碳在碱性条件下反应得到N,N-二甲基二硫代氨基甲酸钠（SDDC）;SDF0和SDDC反应得到双硫化魔芋寡糖素。通过正交实验优化了反应条件。DSOKGM对魔芋软腐病、山药炭疽病、小麦赤霉病、梨黑斑、棉花黄萎、稻瘟等细菌均有抑制作用,具有诱导植物产生植保素的作用,是一种潜在的新型生物农药。     

天津工业生物技术研究所体外合成功能性二糖研究取得进展

功能性二糖是一类具有特殊功效的低聚糖,由两个单糖通过不同糖苷键连接而成,具有高甜度、低卡路里、低升糖指数的特点,可作为益生元和功能性甜味剂用于食品领域.此外,某些功能性二糖还因其独特的功能,被广泛应用于化妆品、生物技术和制药等领域.二糖的传统制备方法是天然聚糖的酸解纯化,但对应的天然聚糖供应有限,且酸解产物复杂,纯化成本很高.随着酶催化技术的发展,人们愈发倾向于寻找合适的酶催化制备二糖.目前,在合成糖苷键方面拥有优良特性的糖苷磷酸化酶逐渐引起关注,但是其催化底物1-磷酸糖价格昂贵,导致合成二糖成本较高.     

寡聚糖生物农药项目获大连科技奖

4月11日从大连化学物理研究所获悉,该所完成的系列寡聚糖生物农药及应用项目获得大连市科学进步一等奖.     

β-甘露聚糖酶的基因与表达

β-甘露聚糖酶(EC 3.2.1.78)是一类能够水解含β-1,4-D-甘露糖苷键的内切水解酶,属于半纤维素酶类。水解的底物有半乳甘露聚糖、葡萄甘露聚糖、半乳葡萄甘露聚糖和甘露聚糖,产物有少量的单糖和2～10个单糖分子构成的寡糖。在纸浆漂白,饲料加工,食品加工等方面具有广阔的应用前景。文章综述了近年来国内外对β-甘露聚糖酶的基因序列、分子的结构区域、基因克隆和表达方面的研究进展。     

基于分子模拟技术研究来源于嗜热地衣芽孢杆菌葡聚糖酶的活性位点

为研究来源于嗜热地衣芽孢杆菌葡聚糖酶与底物的识别机制,本文通过利用分子对接、分子动力学模拟和MM-PBSA计算的方法研究了葡聚糖酶与二聚糖小分子之间的作用机制,试验结果表明,葡聚糖酶与底物的接触数较大并且距离较少,这说明其结合较为紧密;通过能量拆分,我们可以得出,Gly46、Leu63、Gln67、Tyr68、His73、Thr124、Gly125和Gln129是对结合二聚糖的关键氨基酸残基,并且His73和Thr124与二聚糖分子形成了较为稳定的氢键,这将有助于葡聚糖酶与底物的结合。本研究以期为葡聚糖酶分子结构后续的理性改造和高效利用提供有力依据。     

Generation of new derivatives of the antitumor antibiotic mithramycin by altering the glycosylation pattern through combinatorial biosynthesis

Mithramycin is an antitumor drug produced by Streptomyces argillaceus. It consists of a tricyclic aglycone and five deoxyhexoses that form a disaccharide and a trisaccharide chain, which are important for target interaction and therefore for the antitumor activity. Using a combinatorial biosynthesis approach, we have generated nine mithramycin derivatives, seven of which are new compounds, with alterations in the glycosylation pattern. The wild-type S. argillaceus strain and the mutant S. argillaceus M7U1, which has altered D-oliose biosynthesis, were used as hosts to express various "sugar plasmids", each one directing the biosynthesis of a different deoxyhexose. The newly formed compounds were purified and characterized by MS and NMR. Compared to mithramycin, they contained different sugar substitutions in the second (D-olivose, D-mycarose, or D-boivinose instead of D-oliose) and third (D-digitoxose instead of D-mycarose) sugar units of the trisaccharide as well as in the first (D-amicetose instead of D-olivose) sugar unit of the disaccharide. All compounds showed antitumor activity against different tumor cell lines. Structure-activity relationships are discussed on the basis of the number and type of deoxyhexoses present in these mithramycin derivatives.     

基于5-FU开发抗肿瘤药物的最新进展

5-氟尿嘧啶及其衍生物是临床上一类抗瘤谱广、效率高的抗代谢药物。寻求高效低毒、高选择性和高靶向性的5-氟尿嘧啶衍生物是目前抗肿瘤药物研究领域的一个热点。本文对5-氟尿嘧啶的各种结构修饰及其生物活性研究进行了总结,将为5-氟尿嘧啶衍生物的研究产生较大的促进作用。     

Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V,a Gilvocarcin‐Type Antitumor Agent

Polycarcin V, a polyketide natural product of Streptomyces polyformus, was chosen to study structure–activity relationships of the gilvocarcin group of antitumor antibiotics due to a similar chemical structure and comparable bioactivity with gilvocarcin V, the principle compound of this group, and the feasibility of enzymatic modifications of its sugar moiety by auxiliary O‐methyltransferases. Such enzymes were used to modify the interaction of the drug with histone H3, the biological target that interacts with the sugar moiety. Cytotoxicity assays revealed that a free 2′‐OH group of the sugar moiety is essential to maintain the bioactivity of polycarcin V, apparently an important hydrogen bond donor for the interaction with histone H3, and converting 3′‐OH into an OCH₃ group improved the bioactivity. Bis‐methylated polycarcin derivatives revealed weaker activity than the parent compound, indicating that at least two hydrogen bond donors in the sugar are necessary for optimal binding.     

Recent Advances in the Discovery of Multitargeted Tyrosine Kinase Inhibitors as Anticancer Agents

The treatment of cancer has been one of the most significant challenges for the medical field. Further research on the signal transduction pathway of tumor cells is driving the rapid development of antitumor agents targeting tyrosine kinases. However, most of the currently approved tyrosine kinase inhibitors based on the “single target/single drug” design are becoming less and less effective in the treatment of complex, heterogeneous, and multigenic cancers; this also results in resistance to chemotherapy. In contrast, multitargeted tyrosine kinase inhibitors (MT-TKIs) can effectively block multiple pathways of intracellular signal transduction. Therefore, they have therapeutic advantages over single-targeted inhibitors and have become a hotspot in antitumor drug research in recent years. This minireview summarizes recent advances in the discovery of MT-TKIs based on their chemical structures. In particular, we describe the kinase inhibitory and antitumor activity of promising compounds, as well as their structure – activity relationships (SARs).     

卡拉胶的生物活性及分子修饰研究进展

卡拉胶作为一种结构独特的硫酸多糖,具有多种生物活性,但因分子量过大,使其在生物医药领域的应用受到限制。文章简要介绍了近年来有关卡拉胶抗病毒、抗肿瘤、抗凝血等生物活性的研究,进一步介绍了卡拉胶分子修饰及其衍生物生物活性的研究进展。     

Regioselective Enzymatic Acylation of Aureolic Acids to Obtain Novel Analogues with Improved Antitumor Activity

A variety of aureolic acids was efficiently obtained by lipase‐catalyzed regioselective acylation reactions of mithramycin and its analogues mithramycin SK and mithramycin SDK. The acylation took place in the aglycone moiety or in the B sugar unit, depending on the substrate, lipase and acyl donor considered. Most of the novel acylated derivatives showed antitumor activity at double digit nanomolar concentrations, in some cases significantly improving the activity of the parent drugs.     

钌及其配合物应用研究进展

钌及其配合物具有较好的催化活性及抗肿瘤活性,在化工及医学领域的应用较广泛。查阅大量相关资料,对其在催化方面及抗肿瘤等领域的研究现状进行综述。     

呋喃甾烷型皂苷的研究进展

呋喃甾烷型皂苷是一类重要的有机化合物,在抗肿瘤、抗病毒、抗菌、抗氧化以及降低血清中的胆固醇方面具有良好的生理活性。文章主要介绍了呋喃甾烷型皂苷的生理活性研究和合成研究进展,为该类化合物的相关研究提供参考。     

京尼平及其衍生物抗阿尔兹海默病作用的研究进展

京尼平(Genipin)是具有环烯醚萜结构的化合物,具有抗血栓、降血糖、抗肿瘤、抗炎和抗老年痴呆等多种药理活性.近年来,人们通过对其结构进行修饰改造,获得了一系列具有抗阿尔兹海默病(AD)活性的京尼平衍生物.对京尼平及其衍生物抗阿尔兹海默病作用的研究进展进行综述,为京尼平的开发利用提供依据.