GLYCOBIOLOGY OF SULFATED GLYCOCONJUGATES IN CANCER

最近对与Canceir相关的糖脂和 含有硫酸盐残基(或残基)的糖蛋白 重要而有趣的问题：异常的硫酸盐化是一种 某些恶性肿瘤的特征；哪种类型的磺基转移酶 是否参与了这些磺基糖偶联物的表达？这 该项目以磺糖的糖生物学为中心，以便 寻求这些问题的答案。最大的利益在于 生物化学方面，以及碳水化合物结构的合成 是这些研究所必需的。正在研究的是不同的 磺基转移酶，如：(A)半乳糖3-0-磺基转移酶， 作用于Gal 0 1-3GaInAca连接的化合物。这一点的存在 人卵巢组织和人脾中的酶活性已经 在这项研究的早期阶段已经得到了证实。(B) 作用于GaIPl-4GlcNAc和Galpl-3GlcNAc的磺基转移酶 分别给出SE-3GaI01-4GIcNAc和SE-3Gal0I-6GIcNAc。人类 结肠组织中含有这种酶。(C)涉及6-0-磺基转移酶 在6‘-磺化的Lewis(X)部分的组装中 [NeuAca2-3(SE-6Gal)pl-4(Fucal-3)GlcNAc]。(D)磺基转移酶， 作用于G1cNAc0I-3GaIP1-OMe得到SE-6GIcNAc0l-3GaI0l-OMe。 不同的肿瘤细胞系和正常组织和癌变组织 被用作筛选和演示 磺基转移酶的存在。在这些来源中，那些展示的 可感知的活动将成为进一步学习的候选对象。这个 硫酸盐位于不同位置的合成糖类 (异构体硫化糖)预计将特别有用 作为表征和分析的参比化合物 磺基转移酶产物。磺基转移酶的鉴定 这些活动将为生物合成途径提供新的线索 糖结合物，尤其是那些含有硫酸盐的糖结合物， 岩藻糖和唾液酸。这些研究将为以下方面提供信息 细胞黏附靶标配体(选择素)的合成 分子。

Recent recognition of canceir-associated glycolipids and glycoproteins containing a sulfate residue (or residues) raises very important and interesting questions: Is aberrant sulfation a characteristic of certain malignancies; what type of sulfotransferases are involved in the expression of these sulfoglycoconjugates? This project centers at the glycobiology of sulfosaccharides in order to seek answers to these questions. The prime interest is in the biochemical aspects, and in the synthesis of carbohydrate structures required for these studies. Under study are different sulfotransferases such as: (a) Galactose 3-0-sulfotransferase, which acts upon Gal 0 1-3GaINAca-linked compounds. The existence of this enzyme activity in human ovarian tissues and human spleen has already been demonstrated in an earlier phase of this research. (b) Sulfotransferase capable of acting on GaIPl-4GlcNAc and Galpl-3GlcNAc to give SE-3GaI0l-4GIcNAc; and SE-3Gal0I-6GIcNAc, respectively. Human colon tissues contain this enzyme. (c) 6-0-Sulfotransferase involved in the assembly of the 6'-sulfated Lewis (x)moiety [NeuAca2-3(SE-6Gal)pl-4(Fucal-3)GlcNAc]. (d) Sulfotransferase, which acts on G1cNAc0I-3GaIP1-OMe to give SE-6GIcNAc0l-3GaI0l-OMe. Different tumor cell lines and both normal and cancerous human tissues are utilized as a source material for screening and demonstrating the existence of sulfotransferase. Among these sources, those displaying appreciable activity become candidates for further study. The synthetic saccharides having sulfate situated at different positions (isomeric sulfated saccharides) are expected to be particularly useful as reference compounds for the characterization and analysis of sulfotransferase products. The identification of sulfotransferase activities will shed new light on the biosynthetic pathways of glycoconjugates, especially those glycoconjugates containing sulfate, fucose and sialic acid. These studies will provide information toward the synthesis of target ligands for cell- adhesion (selectin) molecules.