Rational Design of a Red Fluorescent Sensor for ALDH1A1 Displaying Enhanced Cellular Uptake and Reactivity

Bioconjug Chem. 2020 Feb 19;31(2):224-228. doi: 10.1021/acs.bioconjchem.9b00723. Epub 2019 Nov 18.

Abstract

High aldehyde dehydrogenase 1A1 (ALDH1A1) activity has emerged as a reliable marker for the identification of both normal and cancer stem cells. To facilitate the detection, molecular imaging, and sorting of stem cells, a green fluorescent probe based on the xanthene dye scaffold was recently developed. However, green dyes are less amenable to multicolor imaging because most commercial reagents are also green. Overcoming this limitation will enable the simultaneous tracking of multiple stem cell markers. Herein, we report the development of a red congener, red-AlDeSense. Through chemical tuning we were able to achieve excellent isoform selectivity and chemostability, a good turn on response, and enhanced cellular uptake and reactivity. Importantly, red-AlDeSense represents one of only a few turn-on sensors in the red region that use the d-PeT quenching mechanism. By employing red-AlDeSense and a green anti-CD44 antibody, we were able to demonstrate staining of these two stem cell markers is independent of one another in A549 lung adenocarcinoma cells.

Publication types

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

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / diagnostic imaging
  • Adenocarcinoma of Lung / enzymology*
  • Aldehyde Dehydrogenase 1 Family / analysis*
  • Fluorescent Dyes / chemistry*
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / enzymology*
  • Molecular Imaging
  • Neoplastic Stem Cells / enzymology
  • Optical Imaging
  • Retinal Dehydrogenase / analysis*
  • Xanthenes / chemistry*

Substances

  • Fluorescent Dyes
  • Xanthenes
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase