PMID: 7544886Aug 11, 1995Paper

Stereospecificity of human DNA polymerases alpha, beta, gamma, delta and epsilon, HIV-reverse transcriptase, HSV-1 DNA polymerase, calf thymus terminal transferase and Escherichia coli DNA polymerase I in recognizing D- and L-thymidine 5'-triphosphate as substrate

Nucleic Acids Research
F FocherS Spadari

Abstract

L-beta-Deoxythymidine (L-dT), the optical enantiomer of D-beta-deoxythymidine (D-dT), and L-enantiomers of nucleoside analogs, such as 5-iodo-2'-deoxy-L-uridine (L-IdU) and E-5-(2-bromovinyl)-2'-deoxy-L-uridine (L-BVdU), are not recognized in vitro by human cytosolic thymidine kinase (TK), but are phosphorylated by herpes simplex virus type 1 (HSV-1) TK and inhibit HSV-1 proliferation in infected cells. Here we report that: (i) L-dT is selectively phosphorylated in vivo to L-dTMP by HSV-1 TK and L-dTMP is further phosphorylated to the di- and triphosphate forms by non-stereospecific cellular kinases; (ii) L-dTTP not only inhibits HSV-1 DNA polymerase in vitro, but also human DNA polymerase alpha, gamma, delta and epsilon, human immunodeficiency virus reverse transcriptase (HIV-1 RT), Escherichia coli DNA polymerase 1 and calf thymus terminal transferase, although DNA polymerase beta was resistant; (iii) whereas DNA polymerase beta, gamma, delta and epsilon are unable to utilize L-dTTP as a substrate, the other DNA polymerases clearly incorporate at least one L-dTMP residue, with DNA polymerase alpha and HIV-1 RT able to further elongate the DNA chain by catalyzing the formation of the phosphodiester bond between the incorporate...Continue Reading

References

Dec 1, 1977·European Journal of Biochemistry·U HübscherS Spadari
Apr 29, 1994·Biochemical and Biophysical Research Communications·T YamaguchiM Saneyoshi

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Citations

Dec 19, 2000·Biochemical and Biophysical Research Communications·T YamaguchiM Saneyoshi
Jun 16, 2004·Antiviral Research·Youhoon Chong, Chung K Chu
Mar 31, 2000·Pharmacology & Therapeutics·A A KrayevskyM V Jasko
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Apr 16, 2003·European Journal of Biochemistry·Claudia PastiDominique Deville-Bonne
Feb 10, 2000·Nucleic Acids Research·V V SosunovA A Krayevsky
Mar 26, 2003·Nucleic Acids Research·Christian FrauendorfSven Klussmann
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Dec 20, 2000·Antimicrobial Agents and Chemotherapy·M L BryantJ P Sommadossi
Aug 29, 2003·Biochemical and Biophysical Research Communications·Hidehito UrataMasao Akagi
Jul 5, 2005·Expert Opinion on Investigational Drugs·S SpadariF Focher
Sep 21, 2001·Nucleosides, Nucleotides & Nucleic Acids·T YamaguchiM Saneyoshi
Sep 21, 2001·Nucleosides, Nucleotides & Nucleic Acids·M L BryantJ P Sommadossi
Feb 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Valeria Famiglini, Romano Silvestri
Dec 22, 1999·Journal of Viral Hepatitis·T Shaw, S A Locarnini
Dec 16, 2003·Biochemical and Biophysical Research Communications·Hidehito UrataMasao Akagi
Jun 27, 2000·Gastroenterology·J Torresi, S Locarnini

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