Gabius H J
Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539 München, Germany.
Anat Histol Embryol. 2001 Feb;30(1):3-31. doi: 10.1046/j.1439-0264.2001.00305.x.
The central dogma of molecular biology limits the downstream flow of genetic information to proteins. Progress from the last two decades of research on cellular glycoconjugates justifies adding the enzymatic production of glycan antennae with information-bearing determinants to this famous and basic pathway. An impressive variety of regulatory processes including cell growth and apoptosis, folding and routing of glycoproteins and cell adhesion/migration have been unravelled and found to be mediated or modulated by specific protein (lectin)-carbohydrate interactions. The conclusion has emerged that it would have meant missing manifold opportunities not to recruit the sugar code to cellular information transfer. Currently, the potential for medical applications in anti-adhesion therapy or drug targeting is one of the major driving forces fuelling progress in glycosciences. In histochemistry, this concept has prompted the introduction of carrier-immobilized carbohydrate ligands (neoglycoconjugates) to visualize the cells' capacity to be engaged in oligosaccharide recognition. After their isolation these tissue lectins will be tested for ligand analysis. Since fine specificities of different lectins can differ despite identical monosaccharide binding, the tissue lectins will eventually replace plant agglutinins to move from glycan profiling and localization to functional considerations. Namely, these two marker types, i.e. neoglycoconjugates and tissue lectins, track down accessible binding sites with relevance for involvement in interactions in situ. The documented interplay of synthetic organic chemistry and biochemistry with cyto- and histochemistry nourishes the optimism that the application of this set of innovative custom-prepared tools will provide important insights into the ways in which glycans can act as hardware in transmitting information during normal tissue development and pathological situations.
分子生物学的中心法则将遗传信息的下游流动限制在蛋白质层面。过去二十年来对细胞糖缀合物的研究进展表明，有必要在这一著名的基本途径中增加带有信息决定簇的聚糖天线的酶促生成。人们已经揭示了包括细胞生长与凋亡、糖蛋白的折叠与转运以及细胞黏附/迁移在内的多种令人瞩目的调节过程，并发现这些过程是由特定的蛋白质（凝集素）-碳水化合物相互作用介导或调节的。由此得出的结论是，如果不将糖代码纳入细胞信息传递过程，将会错失众多机会。目前，抗黏附治疗或药物靶向的医学应用潜力是推动糖科学发展的主要动力之一。在组织化学中，这一概念促使引入载体固定化的碳水化合物配体（新糖缀合物），以可视化细胞参与寡糖识别的能力。分离出这些组织凝集素后，将对其进行配体分析测试。由于不同凝集素尽管单糖结合相同但其精细特异性可能不同，组织凝集素最终将取代植物凝集素，从聚糖谱分析和定位转向功能考量。也就是说，这两种标记类型，即新糖缀合物和组织凝集素，能够追踪与原位相互作用相关的可及结合位点。合成有机化学、生物化学与细胞化学和组织化学之间已被证实的相互作用，让人们乐观地认为，这套创新的定制工具的应用将为聚糖在正常组织发育和病理情况下作为信息传递硬件的作用方式提供重要见解。
