GLYCOBIOLOGY OF SULFATED GLYCOCONJUGATES IN CANCER

癌症中硫酸化糖复合物的糖生物学

• 批准号: 2104942
• 负责人: KHUSHI L MATTA
• 金额: $ 22.04万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2104942
• 关键词: carbohydrate biosynthesis; chemical synthesis; clone cells; enzyme activity; glycolipids; glycoproteins; high performance liquid chromatography; mass spectrometry; molecular oncology; nuclear magnetic resonance spectroscopy; sulfates; sulfation; sulfotransferase

Recently, cancer-associated glycolipids and glycoproteins containing sulfate residue (or residues) have attracted much attention. The presence of these sulfated glycoconjugates raises some 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 proposal centers at the glycobiology of sulfosaccharides in order to seek answers to these questions. Our prime interest is in the biochemical aspects, and in the synthesis of carbohydrate structures required for these studies. We propose to study different sulfotransferases such as; (a) Galactose 3-O- sulfotransferase, which acts upon Ga1beta1yields3Ga1NAcalpha yields linked compounds. We have already demonstrated the existence of this enzyme activity in human ovarian tissues and human spleen. (b) Sulfotransferase capable of acting on Ga1beta1 yields 4G1cNAc and Ga1beta1yields3G1cNAc to give SE-3Ga1beta1yields4G1cNAc and SE-3Ga1beta1yields6G1cNAc, respectively. Human colon tissues contain this enzyme. (c) 6-O-Sulfotransferase involved in the assembly of the 6'-sulfated Lewis (x) moiety [NeuAcalpha2 yields 3 (SE-6Ga1)beta1 yields4(Eucalpha1 yields 3) G1cNAc]. (d) Sulfotransferase which acts on G1cNAcbeta1 yields 3 Ga1beta1yields OMe to give SE-6G1cNAcbeta1yields3Ga1beta1yieldsOMe. We are interested in utilizing different tumor cell lines and both normal and cancerous human tissues a source material for screening and demonstrating the existence of sulfotransferase. Among these sources, those displaying appreciable activity will become candidates for further study. Our synthetic saccharides having sulfate situated at different positions (isomeric sulfated saccharides) will be particularly useful as reference compounds for the characterization and analysis of sulfotransferase product. 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. A successful outcome of the proposed program will open various avenues for other important investigations.

最近，癌症相关的糖脂和糖蛋白， 硫酸盐残留物（或残留物）已经引起了很多关注。 存在 这些硫酸化的糖复合物提出了一些非常重要的， 有趣的问题：异常硫酸化是否是某些 恶性肿瘤;哪种类型的磺基转移酶参与了恶性肿瘤的发生。 这些磺基糖缀合物的表达？ 该提案以 糖生物学的磺基甜菜碱，以寻求答案，这些 问题. 我们的主要兴趣是在生物化学方面， 这些研究所需的碳水化合物结构的合成。 我们 建议研究不同的磺基转移酶，如：（a）半乳糖3-O- 磺基转移酶，其作用于Ga 1 β 1产生3Ga 1 NA α， 化合物. 我们已经证明了这种酶的存在 在人卵巢组织和人脾中的活性。 (b)磺基转移酶 能够作用于Ga 1 β 1产生4G 1cNAc，Ga 1 β 1产生3G 1cNAc， 分别得到SE-3Ga 1 β 1产生4G 1 cNAc和SE-3Ga 1 β 1产生6 G1 cNAc。 人体结肠组织含有这种酶。 (c)6-O-磺基转移酶 参与6 '-硫酸化刘易斯（x）部分的组装[NeuAcalpha 2 产生3（SE-6 Ga 1）β 1产生4（Eucalpha 1产生3）G1 cNAc]。 （d）其他事项 作用于G1 cNAc β 1的磺基转移酶产生3 Ga 1 β 1，产生OMe， 得到SE-6 G1 cNAc β 1产率3Ga 1 β 1产率OMe。 我们感兴趣的是利用不同的肿瘤细胞系， 和癌性人体组织作为筛选的源材料， 证明磺基转移酶的存在。 在这些来源中， 那些表现出明显活动的人将成为进一步的候选人。 study. 我们的合成硫酸盐位于不同的 位置（异构的硫酸化的C2 H4）将特别有用， 用于表征和分析的参比化合物 磺基转移酶产物。 磺基转移酶活性的鉴定将为 糖缀合物的生物合成途径，特别是那些 含有硫酸盐、岩藻糖和唾液酸的糖缀合物。 这些研究 将为细胞靶向配体的合成提供信息， 粘附（选择素）分子。 拟议的会议取得圆满成果， 该计划将为其他重要调查开辟各种途径。