DMSA, DMPS AND OTHER ORALLY ACTIVE DITHIOL CHELATORS

所述的水溶性二硫醇络合剂DMSA、DMPS和 DMPA正在被越来越多的人接受和治疗 西方世界。DMSA已被FDA归类为 治疗铅中毒的孤儿药物。DMSA和DMPS是 目前正在接受临床评估，以治疗儿童 血液中铅含量升高。根据NHANES II， 这样的孩子的数量并不少。DMPA似乎非常 有效地防止210钚在肾脏中的蓄积。 210Po是氡的衰变子体。分析程序有 被开发成允许研究这些二硫醇和它们的 生物变形剂。计划分离出这些生物转化体 并确定它们的结构。尿液中的金属络合物 这些二硫醇将被分离并确定其结构。 利用直流等离子体发射光谱分析，金属 在给药后排出的类金属物质将被 按顺序确定的。这是一个跨学科的项目， 其中一位分子生物学、细胞生物学和 药理学将与化学教授互动，以 获取尽可能多的代谢和物理化学信息 这些不寻常的药剂曾用于治疗金属中毒。一种新的 一溴高灵敏、高选择性的分析方法 联苯双胺、高效液相色谱法和荧光法是这些研究的基础。 将研究一种使用这些二硫醇的新方法。 将寻找一种基本金属的二硫醇螯合物，它是 稳定性不如铅、汞或砷二硫醇络合物。因此，当 给出了必需金属络合物，必需金属可能是 被重金属取代，而重金属络合物将被 排泄物。此外，这些二硫醇对生物多样性的影响 内源性硫醇的代谢池，如谷胱甘肽和 将对半胱氨酸进行调查。这些二硫醇可能间接地 影响内源性硫醇的生物合成，并可能具有 在防止其氧化方面具有保护作用。

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.