GLYCOBIOLOGY OF SULFATED GLYCOCONJUGATES IN CANCER

癌症中硫酸化糖复合物的糖生物学

• 批准号: 6123270
• 负责人: KHUSHI L MATTA
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123270
• 关键词: biological products; biomedical resource; carbohydrates; health care; immunology; inflammation; lymphatic system; structural biology

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.

癌症相关糖脂的最新认识 含有硫酸盐残基的糖蛋白（或残基） 重要而有趣的问题：异常硫酸化是一种 某些恶性肿瘤的特征;什么类型的磺基转移酶 参与了这些磺基糖缀合物的表达 这 该项目以磺基甜菜碱的糖生物学为中心， 寻求这些问题的答案。 主要兴趣在于 生物化学方面，以及碳水化合物结构的合成 这些研究所需的。 研究对象不同 磺基转移酶，例如：（a）半乳糖3-0-磺基转移酶，其 作用于Gal 0 1- 3GaIN 3连接的化合物。 存在这种 人类卵巢组织和脾脏中的酶活性已经 在这项研究的早期阶段就已经证明了。 （B） 能够作用于GaIP 1 -4GlcNAc和Galpl-3GlcNAc的磺基转移酶 以分别得到SE-3Gal 01 - 4GlcNAc和SE-3Gal 01 - 6 GlcNAc。 人类 结肠组织含有这种酶。 (c)涉及6-0-磺基转移酶 在6 '-硫酸化刘易斯（x）部分的组装中 [中性粒细胞2 -3（SE-6 Gal）pl-4（Fucal-3）GlcNAc]。 (d)磺基转移酶， 作用于GlcNAc 01 - 3GaI 01-OMe，得到SE-6 GlcNAc 01 - 3GaI 01-OMe。 不同的肿瘤细胞系和正常和癌性人体组织 被用作筛选和展示 磺基转移酶的存在。 在这些来源中，显示 值得注意的活动成为进一步研究的对象。 的 具有位于不同位置的硫酸根的合成的聚碳酸酯 （异构的硫酸化的硫酸酯）预期特别有用， 作为参比化合物，用于表征和分析 磺基转移酶产物。 磺基转移酶的鉴定 活动将揭示新的光的生物合成途径， 糖缀合物，特别是那些含有硫酸盐的糖缀合物， 岩藻糖和唾液酸。 这些研究将提供信息， 细胞粘附靶向配体（选择素）的合成 分子。