HOMOCYSTEINE VASCULAR BIOCHEMISTRY & METABOLISM

同型半胱氨酸血管生物化学

• 批准号: 6478947
• 负责人: Donald Weldon Jacobsen
• 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/6478947
• 关键词: AIDS; bacteria; biological products; biomaterials; biomedical resource; carbohydrates; immunology; infection; inflammation; lymphatic system; structural biology; virus

The intercellular matrix (NtkF) of the marine sponge, Microciona prolifera, is a large proteoglycan that is highly glycosylated, sulfated and contains equal amounts of protein and carbohydrate. There is a protein core from which radiate many arms with a high carbohydrate content. Subunits are linked to each other via carbohydrate-carbohydrate bonds, two epitopes of which have been chemically defined. Hyaluronic acid (HA) is a component of MAF, but until now itsfunctional role has been unclear. We have found that MAR as well as MbA.Fds, have potent inhibitory activity against HIV virally infected lymphoid cells and the inhibitory activity I at levels as low as 0. 1 n-&rograms/ml in the absence of any toxicity. We need to sort out, characterize and compare the components of NLAFds in order to identify those with HIV inhibitory effects. The ones which are anionic, i.e., sulfated disaccharide and sulfated tetrasaccharide, may qualify (there maybe others); since these types of anionic compounds have shown HIV inhibition. If their viral inhibitory activity is based upon charge effects, they may prove useful against other enveloped viruses with protein composition similar to HIV. Our recent studies on sponge have shown that sulfation may be an important modifier of cell functions, such as masking of lectins and modulating reactions between proteoglycans and cell surface receptors. The first batch was M[AFds or lyophilized supernatant derived from ethanolic precipitation of M[AFl (water-dialyzed purified M[AF gel that was lyophilized). The second batch was M[AFl (water-dialyzed and lyophilized purified M[AF gel), which was used to derive M[AFds. The mass spectra and GC retention times indicate five monosaccharides with the following relative abundance: Fuc 14%; Man18%; Gal 32%; GlcU 4.5%; GlcNAc; 31%. Neuraminic acid was checked by a very short time methanolysis and none was detected. The total amount of carbohydrate was calculated to be 3.7% - a very small amount.

海洋海绵Microciona的细胞间基质(NtkF) 增殖，是一种高度糖基化的大蛋白多糖， 硫酸盐化，含有等量的蛋白质和碳水化合物。 有一个蛋白质核心，从它辐射出许多手臂，具有高度的 碳水化合物含量。亚基通过以下方式相互链接 碳水化合物-碳水化合物键，其中两个表位 化学定义的。透明质酸(HA)是MAF的一种成分，但 到目前为止，它的功能作用还不清楚。我们发现3月份 和MbA.Fds一样，对HIV有很强的抑制活性 病毒感染的淋巴样细胞及其抑制活性 低至0的水平。在无任何毒性的情况下，每毫升1毫克。 我们需要整理、描述和比较NLAFds的组成部分 以确定那些具有HIV抑制作用的药物。就是那些 它们是阴离子的，即硫酸双糖和硫酸盐化 四糖，可能符合条件(可能还有其他类型)；因为这些类型 许多阴离子化合物都显示出抑制艾滋病毒的作用。如果他们的病毒 抑制活性是基于电荷效应，他们可能会证明 对具有蛋白质组成的其他包膜病毒有用 类似于HIV病毒。我们最近对海绵的研究表明， 硫酸盐化可能是细胞功能的重要修饰物，例如 凝集素的掩蔽及其调节蛋白多糖与蛋白质之间的反应 细胞表面受体。第一批是M[AFDs或冻干 M[AFL]乙醇沉淀上清液 (水透析纯化的M[冻干的AF凝胶]。第二 批次为M[AFL(水透析和冷冻干燥的纯化M[AF凝胶])， 它被用来得到M[AFD.质谱图与GC保留值 时间表明有五种单糖与下列相对分子 丰度：Fuc 14%；Man18%；Gal 32%；Glcu 4.5%；GlcNAc；31%。 神经氨酸是通过很短时间的甲醇分解得到的，没有 被检测到。碳水化合物的总量被计算为 3.7%--这是一个非常小的数字。