ThecycloSal-Nucleotide Delivery System

Development of Chemical Trojan Horses as Antiviral Agents
  • Chris Meier
  • Jan Balzarini
  • Astrid Meerbach
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogs against different viral diseases and cancer chemotherapy. Moreover, pronucleotides are valuable tools for studies concerning nucleoside/nucleotide metabolism. The basic idea is to achieve nucleotide delivery into cells, bypassing limitations with intracellular formation of nucleotides from their nucleoside precursors. The cycloSaligenyl (cycloSal) concept is one of several pronucleotide systems reported so far but is the only approach in which a pronucleotide is cleaved successfully by simple but selective chemical hydrolysis. Beside others, for the nucleoside analog 2′,3′-dideoxy-2′,3′-didehydrothymidine (d4T), the application of the cycloSal approach improved antiviral potency. The basic concept, the chemistry, different structural modifications, and their effects on the antiviral potency of the cycloSal-d4T 5′-monophosphate triesters are discussed. The application of the approach to different biologically active nucleoside analogs against different targets is discussed. First results of a conceptual extension of the original cycloSal approach are summarized. Once the pronucleotides have passed the membrane, the aim is to trap the cycloSalphosphate triesters inside the cells. Therefore, enzyme-cleavable groups have been attached via a linker to the cycloSal moiety.


Antiviral Activity Adefovir Dipivoxil Chemical Hydrolysis Acyclic Nucleoside Phosphate Diester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Chris Meier
    • 1
  • Jan Balzarini
    • 2
  • Astrid Meerbach
    • 3
  1. 1.Institute of Organic ChemistryUniversity of HamburgHamburgGermany
  2. 2.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium
  3. 3.Institute for Virology and Antiviral TherapyJenaGermany

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