Use of a deoxynojirimycin–fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes

Akihiko Hatano, Yuichi Kanno, Yuya Kondo, Yuta Sunaga, Hatsumi Umezawa, Koji Fukui

Research output: Contribution to journalArticle

Abstract

Molecules designed for cell-specific imaging were studied, taking advantage of an enzyme–inhibitor interaction. 1-Deoxynojirimycin (DNJ) can be actively captured by cells which express the surface membrane protein α-glucosidase. New probes composed of DNJ for recognition linked to a fluorophore signal portion were prepared (DNJ-CF 3 1, DNJ-Dans 2 and DNJ-DEAC 3). Docking simulations revealed that the inhibitors acarbose and miglitol and the inhibitor portion of the probes bind at the same position in the pocket of α-glucosidase (human-derived PDB: 3TON). The ability of probes 1–3 to detect the difference between HeLa cells (from human cervical cancer tissue), Neuro-2a cells (from a mouse neuroblastoma C1300 tumor), N1E-115 cells (from a mouse brain neuroblastoma C1300 tumor), A1 cells (from the astrocyte of a newborn mouse brain), and Caco-2 cells (from a human colon carcinoma) was evaluated, and cell-specific fluorescence imaging was possible for conjugate probes 1 and 2. Caco-2 cells treated with probes 1 and 2 showed blue and green fluorescence, respectively, from the cell membrane, and did not stain the Caco-2 cells inside. These results show that DNJ-CF 3 1 and DNJ-Dans 2 recognize an α-glucosidase protein on the surface of Caco-2 cells. Probes 1 and 2 did not stain any part of the other cells. This cell-specific imaging strategy is applicable for a variety of therapeutic agents for many diseases.

Original languageEnglish
Pages (from-to)859-864
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume27
Issue number5
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

1-Deoxynojirimycin
Glucosidases
Cell membranes
Imaging techniques
miglitol
Tumors
Brain
Coloring Agents
Fluorescence
Acarbose
Fluorophores
Membrane Proteins
Tissue
Molecules
Caco-2 Cells

Keywords

  • 1-Deoxynojirimycin
  • Cell-specific imaging
  • Fluorescence
  • Membrane protein
  • Probe

ASJC Scopus subject areas

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

Cite this

Use of a deoxynojirimycin–fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes. / Hatano, Akihiko; Kanno, Yuichi; Kondo, Yuya; Sunaga, Yuta; Umezawa, Hatsumi; Fukui, Koji.

In: Bioorganic and Medicinal Chemistry, Vol. 27, No. 5, 01.03.2019, p. 859-864.

Research output: Contribution to journalArticle

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