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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
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Nucleoside diphosphate and triphosphate prodrugs - An unsolvable task?
1Organic Chemistry, Department of Chemistry, Faculty of Sciences, Universität Hamburg, Hamburg, Germany.
Antiviral Chemistry & Chemotherapy
|November 4, 2017
Summary
This review summarizes advances in nucleoside triphosphate prodrugs using enzymatic triggers for improved intracellular delivery. These prodrugs bypass cellular phosphorylation steps, enhancing antiviral efficacy by avoiding degradation.
Area of Science:
- Nucleoside chemistry
- Prodrug development
- Antiviral drug delivery
Background:
- Previous work established the cycloSal-approach for nucleoside monophosphate delivery.
- Nucleoside di- and triphosphate delivery requires different strategies than monophosphates.
Purpose of the Study:
- To review recent advances in nucleoside di- and triphosphate prodrug development.
- To present novel prodrug systems for enhanced intracellular delivery of nucleotides.
Main Methods:
- Development of prodrugs with lipophilic modification on the terminal phosphate.
- Utilizing enzymatic trigger mechanisms involving (carboxy)esterases for prodrug activation.
- Chemical synthesis and characterization of novel prodrugs.
Main Results:
- New prodrug systems enable direct delivery of di- and triphosphates, bypassing cellular phosphorylation.
- Prodrugs feature lipophilic modifications and long aliphatic residues for optimal delivery.
- Structure-activity relationships and antiviral activity data were evaluated.
Conclusions:
- Nucleoside triphosphate prodrugs offer a bypass for essential phosphorylation steps.
- These prodrugs circumvent enzymatic degradation pathways, potentially increasing antiviral potency.
- The described prodrug strategies represent significant advances in nucleotide-based drug delivery.
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