Abstract
A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations. The analog, [13C6,D8]2DG, showed 13% polarization in solution (27,000-fold signal enhancement at the C1 site), following a dissolution-DNP hyperpolarization process. The phosphorylation of this analog by yeast hexokinase (yHK) was monitored in real-time with a temporal resolution of 1 s. We show that yHK selectively utilizes the β anomer of the 2DG analog, thus revealing a surprising anomeric specificity of this reaction. Such anomeric selectivity was not observed for the reaction of yHK or bacterial glucokinase with a hyperpolarized glucose analog. yHK is highly similar to the human HK-2, which is overexpressed in malignancy. Thus, the current finding may shed a new light on a fundamental enzyme activity which is utilized in the most widespread molecular imaging technology for cancer detection – positron-emission tomography with 18F-2DG.
| Original language | English |
|---|---|
| Article number | 19683 |
| Journal | Scientific Reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Dec 2019 |
Bibliographical note
Funding Information:The authors thank Dr. Ayelet Gamliel for assistance with preparation of formulation for hyperpolarization and David Shaul for assistance in NMR spectral acquisitions. This project has received funding from the European Research Council (ERC) under grant agreement No. 338040, the European Union’s Horizon 2020 research and innovation program under grant agreement No. 667192, and from the Israel Innovation Authority, KAMIN Incentive program, grant agreement No. 63361.
Publisher Copyright:
© 2019, The Author(s).
