Executive Summary
Herpes simplex virus type-1 thymidine kinase (HSV1-TK) is an enzyme that phosphorylates a wide range of nucleoside analogs, and has been used as a reporter gene with a variety of radiolabeled nucleotide analogs for positron emission tomography (PET). However, the complexity of synthesizing radiolabel probes and their short lifetime, limits the accessibility of investigating the therapeutic use of HSV1-TK as a reporter gene. MSU researchers have developed new enzymatic methods to produce 5-MDHT, an excellent CEST-MRI probe for imaging the activity of (HSV1-TK). These new methods are eco-friendly, and allow the efficient production of 5-MDHT in a single or two step reactions.
Description of Technology
The technology involves both single and two step reaction methods for making 5-methyl-5,6-dihydrothymidine (5-MDHT). In the single-step method, 5-MDHT is synthesized via a catalyzed base-exchange reaction between 5,5-dimethyl-1,3-diazinane-2,4-dione and 2'-deoxyinosine or thymidine. The two step reaction process involves a base-exchange catalyzed reaction between 5-methyl-5,6-dihydrouracil and 2'-deoxyinosine or thymidine, followed by a methylation step using a S-adenosylmethionine (SAM) yielding 5-MDHT. Reactions take place at slightly higher than room temperature for 6 hours, yielding ≥95% pure 5-MDHT.
Benefits
Applications
Patent Status
Patent pending
Publications
“Biocatalytic Construction of a CEST MRI Nucleoside Probe: Synthesis and Evaluation of 5-Methyl-5,6-dihydrothymidine”, BioRxiv, June 25, 2025
Licensing Rights
Full licensing rights available
Inventors
Dr. Assaf Gilad, Dr. Aimen Al-Hilfi
TECH ID
TEC2025-0068