D-Glucose and d-mannose-based metabolic probes. Part 3: Synthesis of specifically deuterated d-glucose, d-mannose, and 2-deoxy-d-glucose

Izabela Fokt, Stanislaw Skora, Charles Conrad, Timothy Madden, Mark Emmett, Waldemar Priebe

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Altered carbohydrate metabolism in cancer cells was first noted by Otto Warburg more than 80 years ago. Upregulation of genes controlling the glycolytic pathway under normoxia, known as the Warburg effect, clearly differentiates malignant from non-malignant cells. The resurgence of interest in cancer metabolism aims at a better understanding of the metabolic differences between malignant and non-malignant cells and the creation of novel therapeutic and diagnostic agents exploiting these differences. Modified d-glucose and d-mannose analogs were shown to interfere with the metabolism of their respective monosaccharide parent molecules and are potentially clinically useful anticancer and diagnostic agents. One such agent, 2-deoxy-d-glucose (2-DG), has been extensively studied in vitro and in vivo and also clinically evaluated. Studies clearly indicate that 2-DG has a pleiotropic mechanism of action. In addition to effectively inhibiting glycolysis, 2-DG has also been shown to affect protein glycosylation. In order to better understand its molecular mechanism of action, we have designed and synthesized deuterated molecular probes to study 2-DG interference with d-glucose and d-mannose metabolism using mass spectrometry. We present here the synthesis of all desired probes: 2-deutero-d-glucose, 2-deutero-d-mannose, 6-deutero-d-glucose, 6-deutero-d-mannose, and 2-deutero-2-deoxy-d-glucose as well as their complete chemical characterization.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalCarbohydrate Research
Volume368
DOIs
StatePublished - Mar 7 2013

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Mannose
Glucose
Metabolism
Glycosylation
Molecular Probes
Monosaccharides
Carbohydrate Metabolism
Glycolysis
Antineoplastic Agents
Mass spectrometry
Mass Spectrometry
Neoplasms
Up-Regulation
Genes
Cells
Molecules

Keywords

  • 2-Deutero-2-deoxy-d-glucose
  • 2-Deutero-d-glucose
  • 2-Deutero-d-mannose
  • 6-Deutero-d-glucose
  • 6-Deutero-d-mannose
  • Metabolic probes

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Organic Chemistry

Cite this

D-Glucose and d-mannose-based metabolic probes. Part 3 : Synthesis of specifically deuterated d-glucose, d-mannose, and 2-deoxy-d-glucose. / Fokt, Izabela; Skora, Stanislaw; Conrad, Charles; Madden, Timothy; Emmett, Mark; Priebe, Waldemar.

In: Carbohydrate Research, Vol. 368, 07.03.2013, p. 111-119.

Research output: Contribution to journalArticle

Fokt, Izabela ; Skora, Stanislaw ; Conrad, Charles ; Madden, Timothy ; Emmett, Mark ; Priebe, Waldemar. / D-Glucose and d-mannose-based metabolic probes. Part 3 : Synthesis of specifically deuterated d-glucose, d-mannose, and 2-deoxy-d-glucose. In: Carbohydrate Research. 2013 ; Vol. 368. pp. 111-119.
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