Inhibition of RNA-directed DNA polymerase from avian myeloblastosis virus by a 5-benzyl-6-aminouracil.
5-(p-Chlorobenzyl)-6-aminouracil (5-ClAU) inhibited RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus. Inhibition was expressed only in the presence of a polyribonucleotide template such as mRNA or poly(rA), and kinetic analysis suggested that the action of 5-ClAU is competitive with template:primer. 5-ClAU did not inhibit HeLa DNA polymerase gamma, an enzyme that efficiently copies polyribonucleotide templates. A mechanism is proposed in which a 5-ClAU:template complex interferes with enzyme function, based partly on NMR studies indicating that 5-ClAU can form a hydrogen-bonded complex with deoxyadenosine in solution.
Wright
G E
GE
Brown
N C
NC
D000818:Animals; D001354:Avian Leukosis Virus / Q000201:enzymology*; D009189:Avian Myeloblastosis Virus / Q000201:enzymology*; D002417:Cattle; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors; D013053:Spectrophotometry; D013698:Templates, Genetic; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology
D009838:Oligodeoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D011061:Poly A; D014498:Uracil; C018368:poly(rA).oligo(dT); C044442:5-(4-chlorobenzyl)-6-aminouracil