Tris(2-pyridylmethyl)amine (TPA) as a membrane-permeable chelator for interception of biological mobile zinc
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Lippard_Tris 2-pyridylmethyl.pdf
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1.77 MB
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Author(s)
Huang, Zhen
Zhang, Xiao-an
Bosch, Miquel
Smith, Sarah J.
Lippard, Stephen J.
Date Issued
May 2013
Journal
Metallomics
Publisher
Royal Society of Chemistry, The
Citation
Huang, Zhen, Xiao-an Zhang, Miquel Bosch, Sarah J. Smith, and Stephen J. Lippard. “Tris(2-Pyridylmethyl)amine (TPA) as a Membrane-Permeable Chelator for Interception of Biological Mobile Zinc.” Metallomics 5, no. 6 (2013): 648.
Version
Author's final manuscript
Abstract
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 pK[subscript a], and smaller size. These results demonstrate that TPA chelation is a valuable addition to the methodologies available for investigating mobile zinc in biology.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Chemistry
Picower Institute for Learning and Memory
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1039/c3mt00103b
