TRITIATION OF BETA CYCLODEXTRIN: HEPARIN

具有肝素样活性的药物的基本组成要求 细胞调节活性肝素被认为具有 多种细胞调节活性。 使用compositionally 简单、结构刚性和低分子量糖类 分子（环糊精），我们证明，这些活动 主要取决于一个单一的，总的组成参数： 相邻阴离子（硫酸根）的最小分子内密度 组 同样的关键参数被证明是参与 实现如血管生成一样多样的细胞调节行为， 内皮增殖，抑制平滑肌细胞生长， 和保护细胞免受病毒侵袭。 物理化学 证据表明，关联此属性与多离子 阴离子和阳离子位点簇之间的络合物形成 对络合物的影响 这些观察很早就恢复了 静电络合作用的决定性作用 像肝素这样的糖胺聚糖的能力。 连同 报告了对类肝激素和其他药物的大量观察结果， 细胞生物学和医学的不同专业领域，他们提供 有证据表明，临界阴离子（硫酸盐）密度的分子试剂 （MACAD）代表了一大类分子，与之相反， 蛋白质，不依赖于其细胞生物学的结构细节， 活性，但通过与蛋白质试剂的离子络合作用发挥作用 (e.g.生长因子），从而修饰它们的结构特异性 活动 氚标记这些材料将大大 有助于研究作用机制。 首次试图 通过金属催化交换标记到最终分子中， 不成功。 作为第二种方法，制备适合于氢化物的前体。 正在准备削减，我们希望执行这些措施， 在接下来的一段时间里，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.