Nucleotide probes of DNA polymerases

• Autorzy: Wright G. E.
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

DNA polymerase; active site mutant; nucleotide; mutant; inhibitor

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1996
• Tom: 43
• Numer: 1
• Opis fizyczny: p.115-124,fig.

Twórcy

autor

Wright G. E.

• University of Massachusetts Medical School, Worcester, MA 01655 USA

Bibliografia

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• 3. Misra, U.K., Khan, N.N., Agrawal, S. & Wright, G.E. (1992) Chemical and enzymatic incorporation of N2-(p-n-butylphenyl)-2'-de- oxvguanosine into an oligodeoxyribonucleo- tide. Nucleic Acids Res. 20,4547-4551.
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• 29. Ta lanía n,R., Focher, F., Brown, N., Hiibscher, U., Khan, N. & Wright, G. (1990) DNA polymerase delta: A target for selective inhibitor design; in Molecular Aspects of Chemotherapy (Borowski, H. & Shugar, D., eds.) pp. 105-118, Pergamon Press, Elmford, New York.
• 30. Jansons, J., Verri, A., Focher, F., Stattel, J. & Wright, G.F. (1996) Synthesis and DNA polymerase inhibition by .\r2-(p-w-octylphe- nyl)-2'-deoxyguanosine 5'-triphosphate. Nuc­leoides. Nucleoides 15,669-682.