Tris(2-pyridylmethyl)amine (TPA) as a membrane-permeable chelator for interception of biological mobile zinc

Author(s)
Huang, Zhen; Zhang, Xiao-an; Bosch, Miquel; Smith, Sarah J.; Lippard, Stephen J.
Thumbnail
DownloadLippard_Tris 2-pyridylmethyl.pdf (1.769Mb)
OPEN_ACCESS_POLICY
Terms of use
Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
Metadata
Show full item record
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.
Date issued
2013-05
URI
http://hdl.handle.net/1721.1/95490
Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Chemistry; Picower Institute for Learning and Memory
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
ISSN
1756-5901
1756-591X
Collections