title: D-Glucose and D-mannose-based metabolic probes. Part 3: Synthesis of specifically deuterated D-glucose, D-mannose, and 2-deoxy-D-glucose.
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.
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 1950, Houston, TX 77030, USA.
authors: Izabela
authors: I
authors: Fokt
authors: Stanislaw
authors: S
authors: Skora
authors: Charles
authors: C
authors: Conrad
authors: Timothy
authors: T
authors: Madden
authors: Mark
authors: M
authors: Emmett
authors: Waldemar
authors: W
authors: Priebe
mesh_terms: D003847:Deoxyglucose / Q000138:chemical synthesis* / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry*; D005947:Glucose / Q000138:chemical synthesis* / Q000737:chemistry*; D008358:Mannose / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D003847:Deoxyglucose; D003903:Deuterium; D005947:Glucose; D008358:Mannose
references: J Gen Physiol. 1927 Mar 7;8(6):519-30
references: 19872213
references: Nat Rev Cancer. 2002 Sep;2(9):683-93
references: 12209157
references: Carbohydr Res. 2004 Apr 28;339(6):1173-8
references: 15063207
references: Exp Mol Med. 2010 Nov 30;42(11):777-86
references: 20926918
references: Anticancer Res. 2006 Sep-Oct;26(5A):3561-6
references: 17094483
references: Biochem J. 1979 Oct 15;184(1):113-23
references: 534512
references: Oncogene. 2006 Aug 7;25(34):4633-46
references: 16892078
references: Carbohydr Res. 1977 Sep;58(1):212-6
references: 912680
references: Angew Chem Int Ed Engl. 1999 Nov 15;38(22):3334-3339
references: 10602188
references: Cancer Res. 2004 Jan 1;64(1):31-4
references: 14729604