Alpha,beta-difluoromethylene deoxynucleoside 5'-triphosphates: a convenient synthesis of useful probes for DNA polymerase beta structure and function

Org Lett. 2009 May 7;11(9):1883-6. doi: 10.1021/ol701755k.


Alpha,beta-difluoromethylene deoxynucleoside 5'-triphosphates (dNTPs, N = A or C) are advantageously obtained via phosphorylation of corresponding dNDP analogues using catalytic ATP, PEP, nucleoside diphosphate kinase, and pyruvate kinase. DNA pol beta K(d) values for the alpha,beta-CF(2) and unmodified dNTPs, alpha,beta-NH dUTP, and the alpha,beta-CH(2) analogues of dATP and dGTP are discussed in relation to the conformations of alpha,beta-CF(2) dTTP versus alpha,beta-NH dUTP bound into the enzyme active site.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • DNA Polymerase beta / metabolism*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyadenine Nucleotides / chemical synthesis*
  • Deoxyadenine Nucleotides / chemistry
  • Deoxycytosine Nucleotides / chemical synthesis*
  • Deoxycytosine Nucleotides / chemistry
  • Deoxyguanine Nucleotides / chemical synthesis*
  • Deoxyguanine Nucleotides / chemistry
  • Molecular Probes
  • Molecular Structure
  • Nucleoside-Diphosphate Kinase / metabolism*
  • Pyruvate Kinase / metabolism*
  • Stereoisomerism


  • Deoxyadenine Nucleotides
  • Deoxycytosine Nucleotides
  • Deoxyguanine Nucleotides
  • Molecular Probes
  • deoxyguanosine triphosphate
  • Adenosine Triphosphate
  • Pyruvate Kinase
  • Nucleoside-Diphosphate Kinase
  • DNA Polymerase beta
  • DNA-Directed DNA Polymerase
  • 2'-deoxyadenosine triphosphate