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M9460544.TXT
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1994-06-25
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Document 0544
DOCN M9460544
TI Chiral discrimination of enantiomeric 2'-deoxythymidine 5'-triphosphate
by HIV-1 reverse transcriptase and eukaryotic DNA polymerases.
DT 9408
AU Yamaguchi T; Iwanami N; Shudo K; Saneyoshi M; Department of Biological
Sciences, Nishi-Tokyo University,; Yamanashi, Japan.
SO Biochem Biophys Res Commun. 1994 Apr 29;200(2):1023-7. Unique Identifier
: AIDSLINE MED/94234989
AB Inhibitory effects of 2'-deoxy-L-thymidine 5'-triphosphate (L-dTTP), the
enantiomer of the natural substrate D-dTTP, on the activity of mammalian
DNA polymerases alpha, beta and gamma, Escherichia coli DNA polymerase I
and human immunodeficiency virus 1 (HIV-1) reverse transcriptase were
examined. When poly(rA)n-oligo(dT)12-18 was used as the template-primer,
L-dTTP showed remarkable inhibitory effect on HIV-1 reverse
transcriptase in competitive fashion with respect to the substrate dTTP.
In contrast, L-dTTP did not inhibit DNA polymerases alpha and was
slightly inhibitory to DNA polymerase beta. These results suggest that
the nuclear DNA polymerases alpha and beta showed high specificity for
the substrate with the natural configuration of the sugar moiety,
D-dTTP, exhibiting little or no ability to recognize L-dTTP, whereas
HIV-1 reverse transcriptase essentially lacked the ability to
differentiate the D- and L-sugar moieties.
DE Animal Binding, Competitive Cattle DNA Polymerase I/ANTAGONISTS &
INHIB/METABOLISM DNA Polymerase II/ANTAGONISTS & INHIB/METABOLISM DNA
Polymerases/ANTAGONISTS & INHIB/*METABOLISM HIV-1/*ENZYMOLOGY In Vitro
Kinetics Oligodeoxyribonucleotides/METABOLISM Poly A/METABOLISM Rats
Reverse Transcriptase/ANTAGONISTS & INHIB/*METABOLISM Stereoisomers
Substrate Specificity Thymine
Nucleotides/CHEMISTRY/*METABOLISM/PHARMACOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).