Structure-activity relationships for the inhibition of DNA polymerase alpha by aphidicolin derivatives

Nucleic Acids Res. 1989 Aug 11;17(15):6339-48. doi: 10.1093/nar/17.15.6339.


Aphidicolin and 17 derivatives that have been structurally modified in the A- and D-rings were assessed for their ability to inhibit DNA polymerase alpha. No derivative surpassed the activity of aphidicolin; derivatives with structural alterations in the A-ring exhibited significantly greater loss of activity relative to derivatives with structural alterations in the D-ring. The conclusions of these studies indicate a critical role for the C-18 function in the interaction of aphidicolin with polymerase alpha. Molecular modelling studies could not identify structural features of the aphidicolin-dCTP "overlap" that is unique to dCTP, relative to the remaining dNTPs, and that is consistent with the extant structure-activity data.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aphidicolin
  • Binding Sites
  • DNA Polymerase II / antagonists & inhibitors*
  • Diterpenes / pharmacology*
  • Molecular Conformation
  • Molecular Structure
  • Structure-Activity Relationship


  • Diterpenes
  • Aphidicolin
  • DNA Polymerase II