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) prolifera，是一种高度糖基化的大蛋白聚糖， 硫酸盐，含有等量的蛋白质和碳水化合物。 有一个蛋白质核心，从该核心辐射出许多具有高强度的臂 碳水化合物含量。 子单元通过以下方式相互连接 碳水化合物-碳水化合物键，其中两个表位已被 化学定义的。 透明质酸（HA）是MAF的组成部分，但是 到目前为止，其功能作用尚不清楚。 我们发现MAR 以及 MbA.Fds，对 HIV 具有有效的抑制活性 病毒感染的淋巴细胞和抑制活性 I 在没有任何毒性的情况下，浓度低至 0. 1 n-&rograms/ml。 我们需要对NLAFds的组成部分进行梳理、表征和比较 以确定那些具有 HIV 抑制作用的药物。 那些 它们是阴离子的，即硫酸化二糖和硫酸化 四糖，可能符合条件（可能还有其他）；因为这些类型 阴离子化合物已显示出 HIV 抑制作用。 如果他们的病毒 抑制活性是基于电荷效应，他们可以证明 可用于对抗其他具有蛋白质成分的包膜病毒 与艾滋病毒相似。 我们最近对海绵的研究表明 硫酸化可能是细胞功能的重要调节剂，例如 凝集素的掩蔽和蛋白聚糖之间的调节反应 细胞表面受体。 第一批是 M[AFds 或冻干 源自 M[AFl 的乙醇沉淀的上清液 （水透析纯化的 M[AF 凝胶，冻干）。 第二个 批次是M[AFl（水透析和冻干纯化的M[AF凝胶）， 用于导出 M[AFds。 质谱和 GC 保留 次表示五种单糖，其相对关系如下 丰度：Fuc 14%；男性18%；加仑 32%；葡萄糖4.5%； GlcNAc； 31%。 通过非常短时间的甲醇分解检查神经氨酸，并且没有 被检测到。 碳水化合物总量计算为 3.7%——一个非常小的数量。