TPEN
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IUPAC name
N,N,N′,N′-Tetrakis(2-pyridinylmethyl)-1,2-ethanediamine
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3D model (JSmol)
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| Properties | |
| C26H28N6 | |
| Molar mass | 424.55 g·mol−1 |
| Appearance | Crystalline solid |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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| Infobox references | |
TPEN (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine) is an intracellular membrane-permeable ion chelator for zinc. Chelators can be used in chelation therapy to remove toxic metals in the body. TPEN is a chelator that has a high affinity for zinc. For example, one study showed that TPEN is a stronger chelator compared to other chelators like pentetic acid (DTPA) when high levels of zinc are present (15 µM). When low levels of zinc were present however (0, 3, 6, 9 and 12 µM zinc), there was no significant difference. TPEN is a hexadentate ligand which also forms complexes with other soft metal ions such as Cd2+.
In addition to a heavy metal chelator, TPEN is also known to be an inducer of apoptosis., thus it may be toxic to cells. One study showed that depletion of zinc by TPEN induced apoptosis in liver cells of rats. This may be because zinc is necessary for normal functioning of the body; for example, zinc acts as a cofactor for enzymes such as insulin-degrading enzyme. Zinc deficiency symptoms include growth and development problems, hair loss, diarrhea, loss of appetite, and more.
One study showed that TPEN induces translocation of from the mitochondria to the cytosol in human peripheral blood T lymphocytes. This leads to the activation of caspases-3, -8, and -9. When these T lymphocytes were pretreated with caspase inhibitors, DNA fragmentation (an indicator of apoptosis) was prevented. This suggests that apoptosis that is triggered by zinc deficiency is dependent on caspase proteins. Similar results were shown in rat and human thymocytes when TPEN was used. TPEN is also shown to induce apoptosis in K562 cells, and high doses (120 μM) of zinc result in microglial cell deat. One study examined the requirement for p53, a tumor suppressor protein, as an upstream transcription factor in TPEN-induced neuronal apoptosis, and found that depletion of intracellular zinc with TPEN induces apoptosis. Additionally, the same study found that TPEN increased the expression of pro-apoptotic genes and led to the activation of caspase-11, a mammalian protease. These results suggest that the p53 tumor suppressor protein may play a role in regulating TPEN-induced neuronal apoptosis. Although these studies found that TPEN induces apoptosis, another study found that TPEN inhibits sodium dithionite and glucose deprivation (SDGD)-Induced neuronal death by modulating apoptosis.
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