"Lock-in" modified cyclosal nucleotides--the second generation of cyclosal prodrugs

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):939-42. doi: 10.1081/ncn-200059298.

Abstract

A new generation of cycloSal-pronucleotides is presented. CycloSal-d4TMPs have been modified by introduction of an esterase-cleavable site in order to trap them inside cells. Hydrolysis studies in different media (PBS, CEM/0- and liver extracts) and anti-HIV evaluation of separated diastereomers revealed unexpected differences between the isomers.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • Cell Line
  • Chemistry, Pharmaceutical / methods
  • Dideoxynucleotides
  • Drug Design
  • Esterases / chemistry
  • HIV / metabolism
  • HIV Infections / drug therapy
  • Humans
  • Hydrolysis
  • Models, Chemical
  • Mutation
  • Nucleotides / chemistry*
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry*
  • Protein Isoforms
  • Stavudine / analogs & derivatives*
  • Stavudine / chemical synthesis
  • Stavudine / chemistry
  • Stavudine / pharmacology
  • Thymine Nucleotides

Substances

  • Anti-HIV Agents
  • Cyclosaligenyl-2',3'-didehydro-2',3'-dideoxythymidine monophosphate
  • Dideoxynucleotides
  • Nucleotides
  • Prodrugs
  • Protein Isoforms
  • Thymine Nucleotides
  • Stavudine
  • Esterases