Membrane-permeable and -impermeable sensors of the Zinpyr family and their application to imaging of hippocampal zinc in vivo

Carolyn C. Woodroofe, Rafik Masalha, Katie R. Barnes, Christopher J. Frederickson, Stephen J. Lippard

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Esterification of fluorescent biosensors is a common strategy used to trap probes within the cell. Zinpyr-1 (ZP1) is a fluorescein-based bright fluorescent sensor for divalent zinc that is cell permeable without prior modification. We describe here the synthesis and characterization of ZP1 sensors containing a carboxylic acid or ethyl ester functionality at the 5 or 6 position of the fluorescein. The presence of an electronegative carboxylate decreases the proton-induced background fluorescence of the probe by lowering the pK a of the benzylic amines responsible for fluorescence quenching. The charged species ZP1(6-CO 2 -) is membrane-impermeant, whereas the permeability of the neutral ZP1(5/6-CO 2Et) is similar to that of the parent sensor. Intracranial microinfusion of ZP1(6-CO 2Et) into rat hippocampus produces reduced staining of vesicular zinc in neuropil and very clear delineation of zinc-positive injured neuronal somata and dendrites as compared with ZP1.

Original languageEnglish
Pages (from-to)1659-1666
Number of pages8
JournalChemistry and Biology
Volume11
Issue number12
DOIs
StatePublished - 1 Dec 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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