Prodrug Approaches of Nucleotides and Oligonucleotides

Paivi      Poijarvi-Virta; Harri      Lonnberg

Abstract

The main threshold for the therapeutic applications of nucleotides and oligonucleotides is theirionic structure which implies poor cellular uptake and unfavorable pharmacokinetic parameters. To circumventthese problems, the anionic phosphate moieties may be temporarily masked with enzymolabile protectinggroups to form neutral pronucleotides or pro-oligonucleotides. In cells, enzymes cleave the protecting groupsand release the parent drug. Several prodrug strategies have been developed, but the kinetics and mechanismsof the deprotection of potential prodrug candidates are still often poorly known. The purpose of the presentreview is to summarize the current knowledge on the chemical aspects of alternative prodrug strategies atnucleotide and oligonucleotide level.

Keywords: short interfering RNAs, nucleotide prodrug, Bis(POM)-Nucleotides, Cyclic Phosphoramidate Pronucleotides, S-Acyloxymethyl, Protecting Groups

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Current Medicinal Chemistry

Title: Prodrug Approaches of Nucleotides and Oligonucleotides

Volume: 13 Issue: 28

Author(s): Paivi Poijarvi-Virta and Harri Lonnberg

Affiliation:

Keywords: short interfering RNAs, nucleotide prodrug, Bis(POM)-Nucleotides, Cyclic Phosphoramidate Pronucleotides, S-Acyloxymethyl, Protecting Groups

Abstract: The main threshold for the therapeutic applications of nucleotides and oligonucleotides is theirionic structure which implies poor cellular uptake and unfavorable pharmacokinetic parameters. To circumventthese problems, the anionic phosphate moieties may be temporarily masked with enzymolabile protectinggroups to form neutral pronucleotides or pro-oligonucleotides. In cells, enzymes cleave the protecting groupsand release the parent drug. Several prodrug strategies have been developed, but the kinetics and mechanismsof the deprotection of potential prodrug candidates are still often poorly known. The purpose of the presentreview is to summarize the current knowledge on the chemical aspects of alternative prodrug strategies atnucleotide and oligonucleotide level.

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Cite this article as:

Poijarvi-Virta Paivi and Lonnberg Harri, Prodrug Approaches of Nucleotides and Oligonucleotides, Current Medicinal Chemistry 2006; 13 (28) . https://dx.doi.org/10.2174/092986706779010270

DOI https://dx.doi.org/10.2174/092986706779010270	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

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