PAF ACETYLHYDROSE & CONTROL OF PEROXIDATIVE DAMAGE TO SPERM MEMBRANES

PAF乙酰氢

• 批准号: 6206437
• 负责人: JOHN E PARKS
• 金额: $ 0.62万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6206437
• 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.

我们研究了酶辅助合成Ofigo-和 聚-N-乙酰半乳聚糖-fino-聚糖（NALG），一组 也具有信号传导功能的粘附介导蛋白。 NALC-rs与蛋白质和脂质共价连接，特别是在 哺乳动物细胞表面，以及细胞外基质中， 它们被称为硫酸角质素。 它们的粘附功能包括 参与细胞与细胞和细胞与基质介导的结合 通过糖-蛋白质，也可能通过糖-糖 交互. 我们的目标是合成无花果或多糖， NALG型，能够与粘附介导的哺乳动物细胞结合 表面凝集素 能够抑制ce! I-to-cell. 和 细胞与基质的粘附，这种粘附可能成为有用的抗- 消炎、抗感染或避孕药。 它们也可以 作为发展生物学的研究工具很有价值。 大号、 高效价的奥菲戈肽还应引起继发性反应， 在细胞表面聚集合适的反蛋白。 因此，我们认为， 能够诱导不可逆的 精子顶体反应，应成为可用的fiture。 我们的重点是建设一些比较大的， 复杂的低聚糖，但规模相当小。 推进 通过化学和酶进行结构碳水化合物分析 降解，并通过NMR和MS技术，位点特异性标记 积极研究这些结构。 NALG的分步合成 在我们实验室进行了Leloir途径的体外产率 N-连接型、O-连接型或神经纤维连接型的完全双链， 这取决于所使用的底漆。 的结构表征 合成产物和中间体是由降解 方法和NMR光谱在500 MTIz在我们自己的研究所。 近年来，MALDI-M [S]在我国也得到了广泛的应用。 在合作的基础上进行实验;它给出了分子质量， 采用MALDI-PSD和ESI-CID两种检测方法 详细的结构表征。