Synthesis and biochemical evaluation of 2'-deoxy-lin-benzoadenosine phosphates

Biochemistry. 1984 Aug 14;23(17):3868-73. doi: 10.1021/bi00312a012.

Abstract

2'-Deoxy-lin-benzoadenosine has been synthesized via reductive deoxygenation of 2-(beta-D-ribofuranosyl)-8-(methylthio)imidazo[4,5-g]quinazoline. The 5'-mono-, 5'-di-, and 5'-triphosphates have been prepared by chemical and/or enzymatic methods. The 5'-diphosphate was found to be a substrate for phosphorylation by pyruvate kinase and was compared with various natural and extended substrates in kinetic assays. When 2'-deoxy-lin-benzoadenosine 5'-triphosphate was tested in a nick-translation experiment with Escherichia coli DNA polymerase I, a very low level of 32P incorporation from [alpha-32P]TTP into poly[d(AT)] was observed. Nearest-neighbor analysis indicated that the analogue was not significantly incorporated into internal positions in the polymer. In DNA-sequencing reactions, the analogue caused chain termination at adensine residues, although termination was less uniform and less efficient than that with 2',3'-dideoxy-ATP. These experiments show that lin-benzoadenine can form a widened Watson-Crick base pair with thymine. They strongly suggest, though they do not prove, that the enzyme is able to attach the analogue to DNA.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine Nucleotides* / chemical synthesis
  • Adenine Nucleotides* / metabolism
  • Base Sequence
  • Chemical Phenomena
  • Chemistry
  • DNA / metabolism
  • DNA Polymerase I / metabolism
  • Deoxyadenine Nucleotides* / chemical synthesis
  • Deoxyadenine Nucleotides* / metabolism
  • Pyruvate Kinase / metabolism
  • Thymine / metabolism

Substances

  • Adenine Nucleotides
  • Deoxyadenine Nucleotides
  • DNA
  • 2'-deoxy-lin-benzoadenosine monophosphate
  • 2'-deoxy-lin-benzoadenosine diphosphate
  • 2'-deoxy-lin-benzoadenosine triphosphate
  • Pyruvate Kinase
  • DNA Polymerase I
  • Thymine