title: Structure-activity relationships for the inhibition of DNA polymerase alpha by aphidicolin derivatives.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville 22901.
authors.forename: G
authors.initials: G
authors.lastname: Prasad
authors.forename: R A
authors.initials: RA
authors.lastname: Edelson
authors.forename: P D
authors.initials: PD
authors.lastname: Gorycki
authors.forename: T L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D016590:Aphidicolin; D001665:Binding Sites; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D016590:Aphidicolin; D004257:DNA Polymerase II