ANTIMETASTATIC OLIGOSACCHARIDES FROM HYALURONIC ACID

描述：（主要研究者）本提案的主要目的是 为了研究抗转移作用， 通过透明质酸裂解酶（EC 4.2.2.1）作用衍生的寡糖， 透明质酸（HA）。 利用从这些研究中收集的信息， 为设计和合成代谢稳定的 将进行这些寡糖的模拟。 该提案有三个具体目标：（1）分离，纯化， 表征由透明质酸衍生的抗转移寡糖 裂解酶（EC 4.2.2.1）降解HA。 分子量的测定， dp和结构对于开发任何结构活性都很重要 关系（SAR）。 (2)为了研究其他HA降解酶， 它们是来自睾丸组织（EC 3.2.1.35）和水蛭的透明质酸酶 (EC 3.2.1.36），这些产品的结构不同于 的裂解酶。 这些将接受筛选， 抗转移活性，并将充分表征。 (3)使用（1）和（2）中研究开发的SAR， 使它们的-O-键被-CH 2-和-S-战略性地替代， 设计、合成和评估。 我们的策略是利用C-和 S-二糖，其可以糖苷O-连接以提供 合适大小的寡糖以最大化抗转移活性。

DESCRIPTION: (Principal Investigator's) The major aims of this proposal are to investigate the antimetastatic effect that has been observed for certain oligosaccharides derived by the action of hyaluronate lyase (EC 4.2.2.1) on hyaluronic acid (HA). Using information to be gleaned from these studies, a synthetic effort toward designing and synthesizing metabolically stable mimics of these oligosaccharides will be undertaken. The proposal has three Specific Aims: (l) To isolate, purify, and characterize the antimetastatic oligosaccharides derived by hyaluronate lyase (EC 4.2.2.1) degradation of HA. Determination of molecular weight, dp, and structure are important for developing any structure-activity relationships (SAR). (2) To investigate other HA-degrading enzymes, among them hyaluronidases from testicular tissue (EC 3.2.1.35) and from leeches (EC 3.2.1.36) that give products that are different in structure from those of the lyase digests. These will be subjected to screening for antimetastatic activity and will be fully characterized. (3) Using SAR developed from the studies in (1) and (2), oligosaccharides having their -O-linkages strategically replaced by -CH2- and -S- will be designed, synthesized, and evaluated. Our strategy is to make use of C- and S-disaccharides that can be glycosidically O-linked to provide oligosaccharides of appropriate size to maximize antimetastatic activity.