Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Metallomics. 2013 Jun;5(6):648-55. doi: 10.1039/c3mt00103b.
We report the characterization of tris(2-pyridylmethyl)amine (TPA) as a membrane-permeable zinc chelator for intercepting biological mobile zinc. Compared to N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), TPA chelates zinc with faster kinetics in cuvettes, live cells, and brain slices. TPA also is generally less toxic than TPEN in cell culture. Mechanistic analysis indicates that these improvements arise from both the electronic and steric properties of TPA including weaker metal-binding affinity, lower pKa, and smaller size. These results demonstrate that TPA chelation is a valuable addition to the methodologies available for investigating mobile zinc in biology.
我们报告了三(2-吡啶甲基)胺(TPA)作为一种膜通透的锌螯合剂,用于拦截生物可移动锌。与 N,N,N',N'-四(2-吡啶甲基)乙二胺(TPEN)相比,TPA 在试管、活细胞和脑片中与锌的结合动力学更快。TPA 在细胞培养中的毒性通常也低于 TPEN。机制分析表明,这些改进源于 TPA 的电子和空间性质,包括较弱的金属结合亲和力、较低的 pKa 和较小的尺寸。这些结果表明,TPA 螯合是研究生物学中可移动锌的现有方法的一个有价值的补充。