PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES

PAF乙酰氢

• 批准号: 6478966
• 负责人: JOHN E PARKS
• 金额: $ 5.36万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6478966
• 关键词: biological products; biomaterials; biomedical resource; carbohydrates; growth /development; health care; immunology; inflammation; reproductive system; spectrometry; structural biology; technology /technique

We study enzyme-assisted synthesis of ofigo- and poly-N-acetyflactosan-fino-glycans (NALG), a group of adhesion-mediating saccharides that also possess signalling functions. NALC-rs occur in covalent linkage with proteins and lipids, notably on mammalian cell surfaces, and also in extraceUular matrix where some of them are known as keratan sulphates. Their adhesive functions involve participation in cell-to-cell and cell-to-matrix association mediated by saccharide-protein and possibly also by saccharide-saccharide interactions. We aim to synthesize ofigo- or polysaccharides of theNALG-type, capable of binding to adhesion-mediating mammalian cell surface lectins. Being able to inhibit ce!I-to-cell. and cell-to-matrix adhesion, such saccharides may become useful as anti-- Marnmatory, anti-infective or contraceptive agents. They may also be valuable as research tools in advancing developmental biology. Large, ofigovalent ofigosaccharides should also elicit secondary responses by clustering the appropriate counter proteins on cell surfaces. Hence, saccharide-based constructs capable of inducing the irreversible acrosome reaction of sperm, should become available in thefi~iture. Our emphasis is put on construction of many relatively large and complex oligosaccharides, buton a rather modest scale. To advance structural carbohydrate analysis carried out by chemical and enzymatic degradations and by NMR and MS techniques, site-specific labeling of the constructs is actively studied. The stepwise NALG syntheses carried out in our laboratory by the Leloir pathway in vitro yield complete saccharides of N-linked, O-linked or cerwTfide-finked type, depending on the primer used. Structural characterization of the synthesis products and the intermediates is perfon-ned by degradative approaches and by NMR-spectroscopy at 500 MTIz in our own Institute. Recently, MALDI-M[S has also been applied extensively in our experiments on collaborative basis; it gives molecular masses with an admirable precision and sensitivity; MALDI-PSD and ESI-CID are used for detailed structural characterization.

我们研究了ofigo-和的酶辅助合成 聚-N-乙酰半乳糖-菲诺-聚糖 (NALG)，一组 还具有信号功能的粘附介导糖。 NALC-rs 与蛋白质和脂质以共价键连接，特别是在 哺乳动物细胞表面，以及细胞外基质中，其中一些 它们被称为硫酸角质素。 它们的粘合功能包括 参与细胞与细胞和细胞与基质的关联介导 通过糖-蛋白质，也可能通过糖-糖 互动。 我们的目标是合成 ofigo 或多糖 theNALG型，能够结合粘附介导的哺乳动物细胞 表面凝集素。 能够抑制细胞间的作用。 和 细胞与基质的粘附，这样的糖可能会成为有用的抗-- 催产药、抗感染药或避孕药。 他们也可能是 作为推进发育生物学的研究工具很有价值。 大的， 寡价寡糖还应通过以下方式引起二次反应 在细胞表面聚集适当的反蛋白。 因此， 能够诱导不可逆的基于糖的构建体 精子的顶体反应，应该可以在未来实现。 我们的重点是建设许多比较大、比较大的项目。 复杂的寡糖，但规模相当适中。 前进 通过化学和酶法进行结构碳水化合物分析 降解并通过 NMR 和 MS 技术，对 该结构正在被积极研究。 NALG的逐步合成 在我们实验室通过 Leloir 途径进行体外产量 N-连接、O-连接或直链型的完整糖， 取决于所使用的底漆。 结构表征 合成产物和中间体是通过降解法进行的 方法并在我们自己的研究所中通过 500 MTIz 的核磁共振波谱法进行分析。 最近，MALDI-M[S也被广泛应用于我们的 协作实验；它给出了分子质量 令人钦佩的精确度和灵敏度；使用MALDI-PSD和ESI-CID 用于详细的结构表征。