Lack of stereospecificity of some cellular and viral enzymes involved in the synthesis of deoxyribonucleotides and DNA: molecular basis for the antiviral activity of unnatural L-beta-nucleosides

Biochimie. 1995;77(11):861-67. doi: 10.1016/0300-9084(95)90004-7.


Among enzymes involved in the synthesis of nucleotides and DNA, some exceptions have recently been found to the universal rule that enzymes act only on one enantiomer of a chiral substrate and that only one of the enantiomeric forms of chiral molecules may bind effectively at the catalytic site, displaying biological activity. The exceptions include: herpes virus thymidine kinases, cellular deoxycytidine kinase and deoxynucloside mono- and diphosphate kinases, cellular and viral DNA polymerases, such as DNA polymerase alpha, terminal transferase and HIV-1 reverse transcriptase. The ability of these enzymes to utilize unnatural L-beta-nucleosides or -nucleotides as substrate may be exploited from chemotherapeutic point of view.

MeSH terms

  • Antiviral Agents / pharmacology*
  • DNA / biosynthesis
  • DNA-Directed DNA Polymerase
  • Deoxyribonucleotides / biosynthesis
  • Enzymes / metabolism*
  • HeLa Cells
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / enzymology
  • Humans
  • Nucleoside-Phosphate Kinase / chemistry
  • Nucleoside-Phosphate Kinase / metabolism
  • Nucleosides / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thymidine / chemistry
  • Thymidine Kinase / chemistry
  • Thymidine Kinase / metabolism
  • Viral Proteins / metabolism*


  • Antiviral Agents
  • Deoxyribonucleotides
  • Enzymes
  • Nucleosides
  • Viral Proteins
  • DNA
  • Thymidine Kinase
  • Nucleoside-Phosphate Kinase
  • DNA-Directed DNA Polymerase
  • Thymidine