These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Nucleoside diphosphate prodrugs.
    Author: Meier C, Jessen HJ, Balzarini J.
    Journal: Nucleic Acids Symp Ser (Oxf); 2008; (52):83-4. PubMed ID: 18776264.
    Abstract:
    Nucleoside analogs are widely applied in antiviral and antitumor therapy. A severe limitation of these compounds arises from the need of biotransformation to the eventually active nucleoside triphosphates by stepwise addition of phosphate by kinases. This problem can be circumvented by employing reversibly masked nucleotides (prodrugs). However, the known concepts to bypass enzyme activation have almost exclusively been applied to nucleoside monophosphates. Here, we report on the transfer of the bis-(acyloxybenzyl)-concept (BAB-concept) from nucleoside monophosphates to nucleoside diphosphates (NDP) of the anti HIV drugs AZT and d4T. After successful synthesis and isolation of the compounds (BAB-NDPs), it was shown that these compounds exhibit promising hydrolytic properties ranging from high stability at physiological pH to very low stability in cellular extracts. Furthermore, we demonstrated that for some of the compounds a selective cleavage mechanism resulted in the exclusive delivery of the corresponding nucleoside diphosphate within 15 minutes without any degradation of the pyrophosphate unit, which is a unique result in the field of NDP-prodrugs.
    [Abstract] [Full Text] [Related] [New Search]