Studies on the inhibition of Moloney murine leukemia virus reverse transcriptase by N-tritylamino acids and N-tritylamino acid-nucleotide compounds

Nucleosides Nucleotides Nucleic Acids. 2008 Sep;27(9):1011-23. doi: 10.1080/15257770802271698.

Abstract

N-Acylated derivatives of 8-(6-aminohexyl) amino-adenosine-5 '-phosphate were prepared and studied with regard to their effect on DNA synthesis by the Moloney leukemia virus reverse transcriptase. N-palmitoyl and N-nicotinyl derivatives and bis-8-(6-aminohexyl) amino-5'-AMP inhibited the enzyme partially using poly (rA).oligo d(pT)(16-18) as template-primer with [(3)H]dTTP. In order to increase hydrophobicity in the acyl component tethered to the 8-(6-aminohexyl) amino group on the adenine nucleotide, N-trityl-L-phenylalanine and the N-trityl derivatives of the o, m, and p-fluoro-DL-phenylalanine were initially examined for inhibition of the enzyme using the above template-primer system. The compounds all inhibited the reverse transcriptase with IC(50) values of approximately 60-80 microM. However, when N-trityl-m-fluoro-DL-phenylalanine was coupled to the nucleotide 8-(6-aminohexyl) amino-adenosine-5'-phosphate, the inhibitory activity of this compound increased significantly (IC(50) = 5 microM).

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / chemical synthesis
  • Adenosine Monophosphate / metabolism
  • Amino Acids / chemical synthesis
  • Amino Acids / metabolism*
  • DNA / biosynthesis*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Moloney murine leukemia virus / enzymology*
  • RNA-Directed DNA Polymerase / metabolism*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / metabolism*
  • Trityl Compounds / chemical synthesis
  • Trityl Compounds / metabolism*

Substances

  • Amino Acids
  • Reverse Transcriptase Inhibitors
  • Trityl Compounds
  • Adenosine Monophosphate
  • 8-(6-aminohexyl)amino-2'-AMP
  • DNA
  • RNA-Directed DNA Polymerase