[New nucleotide inhibitors of human DNA polymerase alpha]

Mol Biol (Mosk). May-Jun 1995;29(3):689-700.
[Article in Russian]

Abstract

2'-Deoxythymidine 5'-triphosphate and 2'-deoxyadenosine 5'-triphosphate analogs containing a methylene group between the alpha phosphorus and 5' oxygen were synthesized. The substrate properties of these compounds toward some mammalian DNA polymerases and retroviral reverse transcriptases were evaluated using a system containing phage M13mp10 DNA, a synthetic oligonucleotide, and the enzyme. The compounds containing a hydroxyl at the 3' position were incorporated into the DNA chain by DNA polymerase alpha and terminal deoxynucleotidyl transferase, but were not recognized by retroviral reverse transcriptases and mammalian DNA polymerases epsilon and beta. The selectivity of the compounds synthesized was capitalized on during simultaneous isolation of DNA polymerases alpha and epsilon from human placenta. A methylene group was also introduced into the acyclovir molecule. It was shown that this modification inactivates furanose-related nucleotide analogs, but has a minor effect on the substrate properties of acyclic nucleotide analogs.

MeSH terms

  • Animals
  • Base Sequence
  • Cattle
  • DNA Nucleotidylexotransferase / antagonists & inhibitors
  • DNA Nucleotidylexotransferase / metabolism
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA Polymerase II / metabolism
  • DNA Primers
  • Deoxyadenine Nucleotides / chemistry
  • Deoxyadenine Nucleotides / pharmacology*
  • Escherichia coli / enzymology
  • Humans
  • Molecular Sequence Data
  • Substrate Specificity
  • Thymine Nucleotides / chemistry
  • Thymine Nucleotides / pharmacology*

Substances

  • DNA Primers
  • Deoxyadenine Nucleotides
  • Thymine Nucleotides
  • DNA Polymerase II
  • DNA Nucleotidylexotransferase
  • 2'-deoxyadenosine triphosphate
  • thymidine 5'-triphosphate