Nucleotide probes of DNA polymerases.
The modified nucleotides, N2-(p-n-butylphenyl)dGTP and 2-(p-n-butylanilino) dATP and related compounds have been developed as inhibitor-probes of B family DNA polymerases. Synthetic approaches to these compounds are summarized. The nucleotides are potent, non-substrate inhibitors of DNA polymerase a. In contrast, they inhibit other members of the family with less potency but act as substrates for these enzymes. Modelling of the inhibitor: enzyme binding mechanism has been done based on the known structure of E. coli DNA polymerase I, and site-directed mutagenesis experiments to evaluate this mechanism are proposed.
Wright
G E
GE
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA.
D000595:Amino Acid Sequence; D001665:Binding Sites; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D003854:Deoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D008961:Models, Structural; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009711:Nucleotides / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D003854:Deoxyribonucleotides; D004791:Enzyme Inhibitors; D009711:Nucleotides; D004256:DNA Polymerase I; D004257:DNA Polymerase II