A highly sensitive, cell-membrane-permeable fluorescent probe for glutathione

Masafumi Yoshida; Mako Kamiya; Tatsuya Yamasoba; Yasuteru Urano

doi:10.1016/j.bmcl.2014.08.033

A highly sensitive, cell-membrane-permeable fluorescent probe for glutathione

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4363-4366. doi: 10.1016/j.bmcl.2014.08.033. Epub 2014 Aug 20.

Authors

Masafumi Yoshida¹, Mako Kamiya², Tatsuya Yamasoba³, Yasuteru Urano⁴

Affiliations

¹ Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan; Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan.
² Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan.
³ Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan.
⁴ Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113 0033, Japan; Basic Research Program, Japan Science and Technology Agency, Sanbancho-blg, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.

PMID: 25176192
DOI: 10.1016/j.bmcl.2014.08.033

Abstract

Glutathione (GSH) is a primary intracellular antioxidant. Here, we developed a novel, highly sensitive fluorescent probe for GSH, designated DNs-HMRG, whose fluorescence is regulated by two distinct switching mechanisms, intramolecular spirocyclization and photo-induced electron transfer (PeT). DNs-HMRG showed good cell permeability, and a rapid increase in fluorescence intensity was observed when it was applied to living cells. Further, taking advantage of the fact that the intracellular GSH level in tumor tissue is higher than that in normal tissue, we employed this probe for rapid (within a few tens of seconds) in vivo detection of tiny tumor nodules (less than 1mm in diameter) in tumor-bearing mice. This probe is expected be a powerful tool in various biological applications, especially studies on redox status.

Keywords: Fluorescent probe; Glutathione; Intramolecular spirocyclization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Membrane Permeability*
Fluorescence
Fluorescent Dyes / administration & dosage
Fluorescent Dyes / chemical synthesis
Fluorescent Dyes / chemistry*
Glutathione / analysis*
Humans
Mice
Molecular Structure
Neoplasms, Experimental / diagnosis*
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*

Substances

Fluorescent Dyes
Spiro Compounds
Glutathione