TRITIATION OF BETA CYCLODEXTRIN: HEPARIN

类肝素制剂的基本组成要求 肝素的细胞调节活性已被公认为具有 多种多样的细胞调节活动。在作文中使用 简单、结构刚性、低分子量的糖 分子(环糊精)，我们证明了这些活性 主要取决于单一的总体成分参数：a 相邻阴离子(硫酸盐)的最小分子内密度 组。这个相同的关键参数被证明参与了 实现了像血管生成一样多样的细胞调节行为， 血管内皮细胞增殖，抑制平滑肌细胞生长， 以及保护细胞免受病毒入侵。物理化学 有证据表明这一性质与多离子有关。 阴阳离子中心簇之间的络合物形成 关于复杂的合伙人。这些观察结果很早就恢复了。 关于静电络合的决定性作用的建议 糖胺多聚糖的功能，如肝素。加在一起 关于肝素和其他药物的大量观察报告 不同的细胞生物学和医学专业领域，他们提供 有证据表明具有临界阴离子(硫酸盐)密度的分子试剂 (MACAD)代表了一大类分子，与 蛋白质，不依赖于其细胞生物学的结构细节 活性，但功能是通过与蛋白质试剂的离子络合起作用 (例如，生长因子)，从而改变其特定的结构 活动。这些材料的氚标签将大大 促进对作用机制的研究。第一次尝试 通过金属催化交换进入最终分子的标记是 不成功。作为第二种方法，一种适合氢化物的前体 削减正在准备中，我们预计将执行这些 在即将到来的资助期内的反应。

A Basic Compositional Requirement of Agents Having Heparin-Like Cell-Modulating Activities Heparin has been recognized as possessing a large variety of cell-modulating activities. Using compositionally simple, structurally rigid, and low molecular weight saccharide molecules (cyclodextrins), we demonstrated that these activities depend primarily on a single, gross compositional parameter: a minimum intramolecular density of neighboring anionic (sulfate) groups. This same critical parameter is shown to be involved in achieving cell-modulating behaviors as diverse as angiogenesis, endothelial proliferation, inhibition of smooth muscle cell growth, and cell protection against virus invasion. Physical chemical evidence is presented that associates this property with multi-ionic complex formation between the clusters of anionic and cationic sites on the complexing partners. These observations revive early suggestions of the decisive role of electrostatic complexation capabilities of glycosaminoglycans like heparin. Taken together with numerous observations on hepatinoids and other agents reported in diverse specialized fields of cell biology and medicine, they provide evidence that molecular agents of critical anionic (sulfate) density (MACADs) represent a broad class of molecules that, in contrast to proteins, do not rely on structural detail for their cell biological activities, but function by ionic complexation with proteinic agents (e.g. growth factors), thereby modifying their structure specific activities. Tritium labelling of these materials will greatly facilitate studies of the mechanism of action. A first attempt at labelling by metal-catalyzed exchange into the final molecule was unsuccessful. As a second approach, a precursor suitable for hydride reduction is being prepared, and we expect to carry out those reactions during the coming grant period.