Structural and Synthetic studies of biologically active natural glycoconjugates and peptides

对具有生物活性的糖结合物和磷酸肽进行了结构和合成研究，旨在阐明与其功能相关的活性结构和作用机制。从革兰氏阳性肠球菌细胞的脂磷壁酸部分中分离出细胞因子诱导成分，并通过多步层析程序对其化学结构进行了研究。活性成分被证明是不同于典型的已知细菌来源的免疫刺激剂的脂多糖或胞壁肽的新型糖偶联物。我们还研究了另一种从分枝杆菌细胞中提取的具有相似生物学功能的高分子糖结合物。糖苷键的立体选择性结构是化学合成复杂糖结合物的关键问题。通过对硫代糖苷类化合物的选择性活化，建立了几种有效的方法。其中一些方法在…中得到了有效的应用更多关于内毒素糖偶联物的合成工作。在已知的吡啶层合反应的基础上制备双功能荧光试剂，提出了一种新的碳水化合物功能作用的研究方法。用这些试剂标记的碳水化合物适合于用高效液相色谱法进行纯化，然后可以与高分子基质偶联形成新的糖偶联物，这为生物学研究提供了新的途径。化学合成与部分硫化多糖-肝素相对应的特定的硫化双糖。对合成样品的生物学研究表明，这种特殊的二糖组分在肝素与血小板的结合中起着重要的作用。对磷肽的合成研究对于基本理解蛋白质磷酸化的作用是重要的，而蛋白质磷酸化是生命系统中的一个关键过程。研究了保护基团和偶联剂的组合以及合成含磷丝氨酸多肽的反应条件，建立了适用于固相合成和液相合成的高效合成工艺。较少

Structural and synthetic studies were performed on biologically active glycoconjugates and phosphopeptides for the purpose to elucidate the active structures responsible to their functions and the mechanisms of their action. Cytokine-inducing components were isolated and studied for their chemical structures from the lipoteichoic acid fraction of gram positive enterococcal cells through a multistep chromatographic procedure. The active components proved to be novel glycoconjugates different from lipopolysaccharides or muramyl peptides which are typical known immunostimulants of bacterial origin. Another high molecular glycoconjugate with similar biological functions from mycobacterial cells was also investigated.Stereoselective construction of glycosidic linkages is an essential issue for chemical synthesis of complex glycoconjugates. Several efficient methods for this purpose were established by selective activation of thioglycosides. Some of the procedures were applied effectively to … More our synthetic work on endotoxic glycoconjugates. A novel procedure for elucidation of functional role of carbohydrates was also presented by preparation of bifunctional fluorescent reagents based on the known pyridylamination procedure. Labeled carbohydrates with these reagents are suitable for purification with HPLC and can then be coupled with high molecular matrices to form neo-glycoconjugates, which offers new route for biological investigation.Chemical synthesis of a specific sulfated disaccharide corresponding to a partial structure of sulfated polysaccharide, heparin. Biological study with the synthetic specimen led to the conclusion that the particular disaccharide component plays an important role in platelet binding of heparin.Synthetic study of phosphopeptide is important for basic understanding of the role of protein phosphorylation which is now known to be a crucial process in living systems. Reaction conditions as well as combination of protecting groups and coupling reagents were investigated for the preparation of phosphoserine containing peptides to establish efficient procedures applicable to both solid and liquid phase synthesis. Less