Synthesis and Function of Modified Oligosaccharides

为了阐明葡萄糖苷酶和糖基转移酶的反应机理，合成了多种寡糖模拟物，并对其生化行为进行了研究。合成了在非还原端具有5-硫代l -聚焦残基的二糖和三糖，前者被证明是有效的针对α - l -聚焦酶的连锁特异性抑制剂，而后者的一个类似物（H型2）对凝集素和抗体表现出与天然三糖不同的行为。在此基础上，进一步开发了非还原端有偶氮糖的氨基键合成路线。合成了各种糖基转移酶的糖基供体类似物。其中，发现CMP-NeuNAc的UDP-5-thio-GalNAc、GDP-5-thio-L-Fuc和唾液酸盐类似物分别对β -1,4-半乳糖转移酶、α - l - focusyltransferase和α -唾液酸转移酶具有糖基供体活性。

In order to elucidate the reaction machanisms of glucosidases and glycosyltransferases, various oligosaccharide mimics were synthesized and their biochemical behaviors were examined. Di-and trisaccharides having 5-thio-L-fucose residue at the non-reducing end were synthesized and the former analogs were proved to be effective as a linkage-specific inhibitor against alpha-L-fucosidase, while one (H type 2) of the latter analogs showed different behaviors from the natural trisaccharide toward the lectin and antibody. Further, synthetic routes of disaccharides having azasugar at the non-reducing end through amidine linkage were developed. Various glycosyl donor analogs of glycosyltransferases were synthesized. Among them, UDP-5-thio-GalNAc, GDP-5-thio-L-Fuc, and sialyl phosphonate analog of CMP-NeuNAc were found to be active as glycosyl donors, for beta-1,4-galactosyltransferase, alpha-L-fucosyltransferase, and alpha-sialytransferase, respectively.