Chemical modification of oligosaccharide chains of N-aspargine-type glycoproteins

近年来，存在于细胞表面的参与复杂糖缀合的低聚糖链引起了生物化学和有机化学各领域研究者的广泛关注。因此，为了阐明寡糖链的作用，迄今为止进行了大量的研究，并积累了生物学上非常有趣的结果。本研究设计并合成了模拟糖的伪低聚糖，旨在为研究糖苷酶和糖基转移酶在细胞表面聚糖的合成过程中所起的作用提供化学工具。几种含碳糖残基以亚胺键、醚键和硫化物键结合的碳糖双糖和三糖已被合成并进行了生物实验。一般来说，亚胺连接的碳低聚糖被证明对糖苷酶具有抑制作用，而通过醚或硫化物桥连接的碳低聚糖被发现更像是糖基转移酶的底物类似物。本研究结果为酶抑制剂的设计和合成开辟了新的机会。由于碳糖是化学上非常稳定的环醇衍生物，但与真正糖的三维结构非常相似，因此可以对碳糖残基进行不同的化学修饰。目前的研究已与生物化学教授，博士合作。Hindsgaul和Palcic（加拿大阿尔伯塔大学）以及我们合成的具有生物学意义的碳水化合物模拟物似乎有助于他们未来对糖水解酶和重要低聚糖链转移酶的广泛研究。

In recent years, oligosaccharide-chains involved in complex glycoconjugates existing on a cell surface have attracted much attention of many researchers in various fields of biochemistry and organic chemistry. Therefore, in order to elucidate roles of oligosaccharide-chains, extensive studies have so far been carried out, and biologically very interesting results have been accumulated.In the present study, carbohydrate-mimicking pseudo-oligosaccharides were designed and synthesized in order to provide chemical tools which may be useful to study roles of glycosidases and glycosyltransferases involved in biosynthesis of such complex oligosaccharide-chanins fo cell-surface glycanes. Several carba-disaccharides and trisaccharides containing carba-sugar residues bonded by way of imino-, ether and sulfide linkages have been newly synthesized and subjected to biological assay. In general, imino-linked carba-oligosaccharides were shown to possess inhibitory action against glycosidases, whereas the carba-oligosaccahrides linked by ether or sulfide-bridge were found to act rather as substrate analogs toward glycosyltransferases. The present results have opened up new opportunity for the design and synthesis of inhibitors for enzymes. Since carba-sugars are chemically very stable cyclitol derivstives but have close similarlity toward three-dimensional structures of true sugars, different kind of chemical modification may be possibly designed for carba-sugar residues.The present studies have been collaborated with biochemistry professors, Drs.Hindsgaul and Palcic (University of Alberta, Canada), and our synthesized carbohydrate mimics of biological interests seem to assist and contribute to their extensive studies on sugar hydrolases and transferases for important oligosaccharide-chains in future.