Scientists from the University of Pittsburgh have designed nucleoside prodrugs with the potential to act as anti-viral and anti-cancer drugs.
Description
Nucleosides are the structural subunits of nucleic acids like DNA and RNA. Their analogs can be potent therapeutic agents acting as prodrugs requiring a biological phosphorylation reaction sequence to become active. The efficacy of this reaction varies depending on the structure of the nucleosides. Nucleotides, singularly phosphorylated nucleosides, can undergo further phosphorylation more effectively, but challenges exist around their ability to enter cells.
The novel nucleotide prodrugs developed by the team at the University of Pittsburgh are designed to enter target cells as inactive agents and undergo oxidative cleavage only in cells with high levels of oxidative stress, releasing an active nucleotide targeting diseased cells only, overcoming many of the existing challenges with nucleotide prodrugs.
Applications
1. Cancer treatment
2. Anti-viral development
3. Other disease states linked to oxidative stress
Advantages
Previous nucleotide prodrugs have been designed but which rely on enzymatic release in vivo. Not only can these nucleotides lack cell permeability, but can undergo off-target release, decreasing the selectivity of the prodrugs and potentially increasing the risk of side effects.
The novel nucleotide prodrugs reported here use a boryl allyl phosphate group to ensure release in the presence of hydrogen peroxide. Given hydrogen peroxide is formed in areas of high oxidative stress, inherent in the targeted disease tissue, greater selectivity in the targeting of these prodrugs and a reduction in the risk of side effects will be achievable.
Invention Readiness
Currently in the concept phase a nucleotide prodrug that can undergo oxidative cleavage has been designed. Uniquely containing boryl allyl phosphate groups, they have the potential to selectively target diseased cells.
IP Status
https://patents.google.com/patent/WO2024167952A1
