Fluorescent stilbazolium dyes as probes of the norepinephrine transporter

Structural insights into substrate binding

James N Wilson, Adrienne S. Brown, W. Michael Babinchak, Clark D. Ridge, Jamie Walls

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We report the synthesis, binding kinetics, optical spectroscopy and predicted binding modes of a series of sterically demanding, fluorescent norepinephrine transporter (NET) ligands. A series of bulky stilbazolium dyes, including six newly synthesized compounds, were evaluated to determine the effect of extending the molecular probes' 'heads' or 'tails'. Taking advantage of the dyes' characteristic 'turn-on' emission, the kinetic binding parameters, kon and koff were determined revealing that extension of the molecules' tails is well tolerated while expansion of the head is not. Additionally, a 'headfirst' orientation appears to be preferred over a 'tail-first' binding pose. Further details of the possible binding modes were obtained from the emission spectra of the bound probes. A small range of interplanar twist angles, approximately 35° to 60°, is predicted to produce the observed emission. Docking experiments and molecular modelling support the kinetic and spectroscopic data providing structural insights into substrate binding.

Original languageEnglish
Pages (from-to)8710-8719
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number43
DOIs
StatePublished - Nov 21 2012

Fingerprint

norepinephrine
Norepinephrine Plasma Membrane Transport Proteins
transporter
Fluorescent Dyes
Coloring Agents
dyes
Kinetics
probes
Substrates
Head
Molecular Probes
Molecular modeling
Spectrum Analysis
kinetics
Ligands
Molecules
emission spectra
Experiments
ligands
expansion

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Fluorescent stilbazolium dyes as probes of the norepinephrine transporter : Structural insights into substrate binding. / Wilson, James N; Brown, Adrienne S.; Babinchak, W. Michael; Ridge, Clark D.; Walls, Jamie.

In: Organic and Biomolecular Chemistry, Vol. 10, No. 43, 21.11.2012, p. 8710-8719.

Research output: Contribution to journalArticle

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