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

Zhen Huang; Xiao-an Zhang; Miquel Bosch; Sarah J. Smith; Stephen J. Lippard

doi:10.1039/C3MT00103B

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

Zhen Huang,‡^a Xiao-an Zhang,‡^a Miquel Bosch,^b Sarah J. Smith^a and Stephen J. Lippard*^a

* Corresponding authors

^a Department of Chemistry, Massachusetts Institute of Technology, Cambridge, USA
E-mail: lippard@mit.edu
Fax: +1-617-258-8150
Tel: +1-617-253-1892

^b The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, USA

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_a, and smaller size. These results demonstrate that TPA chelation is a valuable addition to the methodologies available for investigating mobile zinc in biology.

Metallomics

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

Abstract

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