DMSA, DMPS AND OTHER ORALLY ACTIVE DITHIOL CHELATORS

水溶性二硫醇螯合剂DMSA、DMPS和 DMPA正在接受越来越多的接受和治疗用途， 西方世界 DMSA已被FDA列为 一种治疗铅中毒的孤儿药。 DMSA和DMPS是 目前正在进行临床评估， 血铅含量升高 根据NHANES II， 这样的孩子数量不小。 DMPA似乎非常 有效防止210钋在肾脏中的积聚。 210Po是氡的衰变产物。 分析方法有 已经开发出允许研究这些二硫醇及其 生物转化体。 计划分离生物转化体 并确定其结构。 尿金属螯合物 分离这些二硫醇并确定其结构。 使用直流等离子体发射光谱法， 而在给予dithoils后排出的类金属， 按顺序确定。 这是一个跨学科的项目， 这是一位分子生物学、细胞生物学和 药理学将与化学教授互动， 获得尽可能多的代谢和理化信息， 这些不寻常的药物用于治疗金属中毒。 一个新 使用一溴化铵的高灵敏度和选择性分析测定 双满、高效液相色谱和荧光法是这些研究的基础。 一种新的方法来使用这些二硫醇将进行调查。 将寻求必需金属的二硫醇螯合物， 比Pb、Hg或As二硫醇螯合物更不稳定。 因此当 必要的金属螯合物，必要的金属可能是 被重金属取代，重金属螯合物将 排泄 此外，这些二硫醇对 内源性硫醇如谷胱甘肽的代谢池， 将研究半胱氨酸。 这些二硫醇可以间接地 影响内源性硫醇的生物合成， 保护作用，防止其氧化。

The water soluble dithiol chelating agent, DMSA, DMPS and DMPA are receiving increasing acceptance and therapeutic use in the Western world. DMSA has been classified by the FDA as an orphan drug for treating lead intoxication. DMSA and DMPS are now undergoing clinical evaluation for treating children with elevated blood levels of lead. According to NHANES II, the number of such children is not small. DMPA appears to be very effective in preventing 210polonium accumulation in the kidney. 210po is a decay daughter of radon. Analytical procedures have been developed to allow the study of these dithiols and their biotransformants. It is planned to isolate the biotransformants and determine their structure. The urinary metal chelates of these dithiols will be isolated and their structure determined. Using direct current plasma emission spectrometry, the metals and metalloids that are excreted after dithoils are given will be determined sequentially. This is an interdisciplinary project in which a Professor of Molecular Biology, Cell Biology and Pharmacology will interact with a Professor of Chemistry to obtain as much metabolic and physico-chemical information about these unusual agents used to treat metal intoxicaton. A new hghly sensitive and selective analytical assay using monobromo bimane, HPLC and fluorescence is the foundation of these studies. A new approach to the use of these dithiols will be investigated. The dithiol chelate of an essential metal will be sought which is less stable than the Pb, Hg or As dithiol chelate. Thus when the essential metal chelate is given, the essential metal might be replaced by the heavy metal and the heavy metal chelate will be excreted. In addition the influence of these dithiols on the metabolci pools of endogenous thiols such as glutathione and cysteine will be investigated. These dithiols may indirectly influence the biosynthesis of endogenous thiols and may have a protective effect in preventing their oxidation.