HIV-1 reverse transcriptase is capable of elongating derivatives of sequence specific noncomplementary oligodeoxynucleotides

Biochem Mol Biol Int. 1998 Aug;45(5):857-64. doi: 10.1002/iub.7510450502.

Abstract

We have carried out a comparison of KM and Vmax values for various primers in the polymerization reaction catalyzed by the HIV-1 RT. The affinity of RT for complementary d(pT)6 containing two different 5'-end pyranone derivatives was 2-3 orders of magnitude higher (KM = 3-15 nM) than that of d(pT)6 (KM = 12.6 mM). Oligodeoxynucleotides (ODNs) noncomplementary to poly(A) template were not elongated by RT. However, derivatives of d(CAGGTG) containing the 5'-terminal chromone and coumarin related groups were efficient primers showing KM (30-300 nM) and Vmax (75-93%) values comparable with that for d(pT)10 (800 nM; 100%). The [d(CAGGTG)]ddT ODN derivatives were effective inhibitors of RT. The primer function of derivatives of noncomplementary ODNs appears to be due to the additional interactions of their 5'-terminal groups with the enzyme tRNA-binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA Primers / metabolism
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / metabolism*
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism*
  • Oligodeoxyribonucleotides / pharmacology
  • Poly T / biosynthesis
  • RNA, Transfer / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology
  • Templates, Genetic

Substances

  • DNA Primers
  • Oligodeoxyribonucleotides
  • Reverse Transcriptase Inhibitors
  • Poly T
  • RNA, Transfer
  • HIV Reverse Transcriptase