Synthesis and characterization of a fluorescent probe for α-tocopherol suitable for fluorescence microscopy

Bioorg Med Chem. 2016 Jun 15;24(12):2754-61. doi: 10.1016/j.bmc.2016.04.044. Epub 2016 Apr 26.

Abstract

Previously prepared fluorescent derivatives of α-tocopherol have shown tremendous utility in both in vitro exploration of the mechanism of ligand transfer by the α-tocopherol transfer protein (α-TTP) and the intracellular transport of α-tocopherol in cells and tissues. We report here the synthesis of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) containing α-tocopherol analog having extended conjugation with an alkenyl thiophene group that extends the absorption and emission maxima to longer wavelengths (λex=571nm and λem=583nm). The final fluorophore thienyl-ene-BODIPY-α-tocopherol, 2, binds to recombinant human α-TTP with a Kd=8.7±1.1nM and is a suitable probe for monitoring the secretion of α-tocopherol from cultured Mcf7#189 cells.

Keywords: BODIPY; Fluorescent ligand; Vitamin E; α-Tocopherol; α-Tocopherol transfer protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron Compounds / chemical synthesis
  • Boron Compounds / chemistry*
  • Boron Compounds / metabolism
  • Carrier Proteins / metabolism
  • Cell Line
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Humans
  • Microscopy, Fluorescence / methods*
  • Protein Binding
  • Rats
  • alpha-Tocopherol / analogs & derivatives*
  • alpha-Tocopherol / analysis*
  • alpha-Tocopherol / metabolism

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Carrier Proteins
  • Fluorescent Dyes
  • alpha-tocopherol transfer protein
  • alpha-Tocopherol