College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People's Republic of China.
Chem Res Toxicol. 2012 Sep 17;25(9):1948-54. doi: 10.1021/tx300265c. Epub 2012 Sep 4.
Poly-α,β-DL-aspartic acid is known as a green chelant of various metal ions. To provide a novel nanochelant for treating Pb(II) poisoning, poly-α,β-DL-aspartic acid was modified with L-Cys to form poly-α,β-DL-aspartyl-L-cysteine (PDC; MW, 27273). DL-Asp was converted into polysuccinimide through a thermal polycondensation, and the amidation of polysuccinimide with L-Cys provided PDC. In water, PDC formed various porous nanospecies. In the mouse lead intoxication model, both intraperitoneal and oral administration of PDC (0.1, 1.0, and 10.0 nmol/kg) dose dependently removed Pb(II) accumulated in the organ, bone, and blood. PDC did not remove the essential metals including Cu(2+), Fe(2+), Mn(2+), Zn(2+), and Ca(2+) of the treated mice. The porous feature and size of the pH- and concentration-dependent nanospecies of PDC benefited the removal of Pb(II).
聚-a，β-DL-天冬氨酸是一种能与各种金属离子形成绿色螯合物的物质。为了提供一种治疗 Pb(II)中毒的新型纳米螯合剂，用 L-半胱氨酸对聚-a，β-DL-天冬氨酸进行了修饰，形成聚-a，β-DL-天冬酰基-L-半胱氨酸（PDC；MW，27273）。通过热缩聚将 DL-Asp 转化为聚琥珀酰亚胺，然后用 L-半胱氨酸对聚琥珀酰亚胺进行酰胺化，得到 PDC。在水中，PDC 形成了各种多孔纳米物质。在小鼠铅中毒模型中，PDC（0.1、1.0 和 10.0 nmol/kg）的腹腔内和口服给药剂量依赖性地去除了器官、骨骼和血液中积累的 Pb(II)。PDC 没有去除治疗小鼠体内的必需金属，包括 Cu(2+)、Fe(2+)、Mn(2+)、Zn(2+)和 Ca(2+)。PDC 的多孔特性和 pH 值及浓度依赖性纳米物质的大小有利于 Pb(II)的去除。
