Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs)

Tomohiro Takasugi, Kenjiro Hanaoka, Ayako Sasaki, Takayuki Ikeno, Toru Komatsu, Tasuku Ueno, Katsuya Yamada, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

Abstract

We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of D-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the fluorophore moiety to a fluorescein analogue, 2-Me TokyoGreen, which is less negatively charged. TokyoGreen-conjugated glucosamines TGG1 and TGG2 were successfully taken up into cells via GLUT. We further derivatized TGG1 and TGG2, and among the synthesized compounds, 2-Me-4-OMe TGG showed weak fluorescence under the acidic conditions of the extracellular environment inside tumors and in gastric cancers, and strong fluorescence at the intracellular physiological pH, under the control of a photoinduced electron transfer (PeT) process. This fluorogenic platform should be useful for developing a range of activatable fluorescent substrates targeting GLUTs, as well as derivatives that would be fluorescently activated by various intracellular enzymes, such as esterases, β-galactosidase and bioreductases.

Original languageEnglish
Pages (from-to)2122-2126
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume27
Issue number10
DOIs
Publication statusPublished - 2019 May 15
Externally publishedYes

Keywords

  • Fluorescent imaging
  • Fluorescent substrates
  • GLUT
  • Glucose
  • Tumor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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